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Notes from the Field: Dr. Ian Tietjen in Africa, Part 3

Written by The Wistar Institute on . Posted in Featured News.

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

If you haven’t started this series with part one, click here.

6 August 2023 – Today we drove to several of the surrounding villages to pick up the healers and take them back to the Shumba Lodge. There were a few groups that went out; my group included Rhona and Jimson Richard as the van driver. Jimson is Richard’s brother and a clerk for the Tutume local government. We went to two villages in the Tutume area, including Mosetse and Maitengwe.

As you can imagine, building trust is essential to establish rapport — which, for me and my colleagues, includes meeting with the family and the leader to discuss how long the elder will be away from the village. We take the time to assure them that we receive no money for these educational sessions and that we always learn as much as is imparted. For this session, we show our healer collaborators how we do biomedical science by running experiments on plant samples. For this visit, we are asking all the healers to refrain from telling us any plant identities and keep all Indigenous or other personal and protected knowledge secret from us.

Our primary goal is to work together to support traditional knowledge with biomedical laboratory resources to better understand natural medicines from many points of view to support healers and their communities. After these meetings, all the families eventually agreed to let the healers go with us; the families even got their photos taken with us. The family’s children are so engaging and fun to talk to.

In total, we have 12 healers from across the region staying with us. There are women and men of all ages: young students just out of university all the way to elders. Some are fluent in English, some know very little, and some know a lot more than they are letting on.

Maitengwe Village
Goats in the Village
Eventually we got all the healers on board and fed everyone dinner in Tutume that evening.

Wistar Researchers Discover Possible New Treatment for Triple-Negative Breast Cancer 

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA—(Sep. 18, 2023)—Zachary Schug, Ph.D., assistant professor in the Molecular and Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, has published a new paper in the journal Nature Cancer. Schug’s paper — titled, “Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer” — demonstrates a double-acting mechanism for fighting a particularly aggressive, difficult-to-treat form of breast cancer. Schug’s research shows how silencing a certain gene, ACSS2, may improve existing treatments for patients.

Triple-negative breast cancer, or TNBC, affects 10-15% of patients with breast cancer in the US. TNBC is called “triple-negative” because the cancer lacks an estrogen receptor, a progesterone receptor, and a HER2 (human epidermal growth factor) receptor. The absence of any of these receptors — receptors that, when present in other forms of breast cancer, can be effectively targeted during treatment — makes treating TNBC quite difficult, and patients with TNBC have limited treatment options. TNBC’s notorious aggression makes the technical challenge of finding a reliably effective treatment target all the more serious: compared to other breast cancers, TNBC grows faster and resists treatment more stubbornly. All these factors contribute to the fact that TNBC patients suffer from worse prognoses.

But Zachary Schug, Ph.D., and co-authors have demonstrated the efficacy of a double-acting concept: silencing the gene ACSS2 impairs TNBC metabolism while simultaneously boosting the immune system’s ability to fight it. ACSS2 regulates acetate, a nutrient that cancer cells — and TNBC cells in particular — take advantage of to grow and spread. Schug and his team used two methods to de-activate ACSS2: CRISPR-Cas9 gene editing, and the compound VY-3-135, a potent ACSS2 inhibitor identified by Schug and his colleagues in 2021.

The researchers found that targeting ACSS2 in this preclinical study not only hampered this aggressive cancer’s ability to metabolize acetate and grow — it also triggered the immune system to recognize and attack the cancer. Because cancer cells with inhibited ACSS2 can’t process acetate very well, the tumor region becomes bathed in acetate, which alerts the immune system of something amiss.

This process of guiding the immune system to the cancer — called “immunosensitization” — has confounded other TNBC researchers. But Schug’s approach showed that ACSS2 inhibition immunosensitized against TNBC so well that tumor growth was drastically reduced, even to the point of wiping out the cancer completely in some experiments.

“Basically, we’ve proved that the immune system can take advantage of acetate that the tumor can’t process. It kicks the cancer while it’s down,” said Schug. “In fact, the immune system does this so well that it remembers how to attack TNBC in the future — even if that tumor’s ACSS2 gene is still active.”

Another group’s different ACSS2-inhibiting approach is in human clinical trials, and Schug’s research shows how ACSS2-inhibiting treatment might be able to improve outcomes for patients diagnosed with the infamous TNBC. By testing ACSS2 inhibitors alongside standard anti-breast-cancer chemotherapy, Schug et al. found that ACSS2 inhibition enhanced the treatment’s effectiveness.

“We knew that ACSS2 was a promising target for TNBC. Our research shows us how the immune effects of ACSS2 inhibition could eventually be used in for TNBC patients with limited treatment options,” said Schug. “More research is needed, but by combining this approach with other cancer therapies, we expect to see big improvements in treating TNBC.”

Co-authors: Katelyn D. Miller, Seamus O’Connor, Katherine A. Pniewski, Toshitha Kannan, Reyes Acosta, Gauri Mirji, Sara Papp, Michael Hulse, Fabrizio Bertolazzi, Yellamelli V. V. Srikanth, Rahul S. Shinde, Daniel T. Claiborne, Andrew Kossenkov, Joseph M. Salvino and Zachary T. Schug of The Wistar Institute; Fabrizio Bertolazzi of the University of Bologna; and Steven Zhao and Kathryn E. Wellen of the University of Pennsylvania.

Work supported by: This work was supported by grants from the National Institutes of Health (NIH) National Cancer Institute (NCI) DP2 CA249950-01, NIH NCI P01 CA114046, NIH R21 CA259240-01, the W.W. Smith Charitable Trust, Susan G. Komen CCR19608782 and the V Foundation for Cancer Research. This research and project is funded, in part, by a contract with the Pennsylvania Breast Cancer Coalition. The PBCC takes no part in and is in no way responsible for any analyses, interpretations or conclusions contained herein. We acknowledge funding from the NIH NCI T32 CA009171 and the American Cancer Society Rena and Victor Damone Postdoctoral Fellowship PF-20-1225-01-CCG. The Wistar Molecular Screening Facility and Genomics Facility are supported by NIH grant P30 CA010815. The Wistar Proteomic and Metabolomic Facility is supported, in part, by NIH grants R50 CA221838 and S10OD023586. The HIC is supported, in part, by NIH P30 AI045008 and P30 CA016520.

Publication information: “Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer” from Nature Cancer

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Notes from the Field: Dr. Ian Tietjen in Africa, Part Two

Written by The Wistar Institute on . Posted in Featured News.

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

If you haven’t started this series with part one, click here.

5 August 2023 – Our combi bus picked us up from the hotel and briefly stopped at the Gaborone airport to retrieve more of our team. We are here to pick up our guests from British Columbia, Canada who have been travelling for almost 48 hours nonstop: Marianne Ignace, Professor of Linguistics at SFU; Dr. Ron Ignace, a retired Chief of the Secwepemc First Nation of British Columbia; and their son Joe Ignace. With them are two Secwepemc traditional healers, Rhona Bowe and Rod Tomma, who are helping us engage and work with traditional healers.

In total, there are 13 of us. The ride from Gaborone to Tutume is mostly a smooth, paved, two-lane road, but it takes about seven hours of driving. The scenery is flat with lots of short, brambly trees; cows, goats, and donkeys amble up and down the side of the highway, and people are selling food, brooms, and gasoline along the side of the road. The sunset is dusty and orange, and it makes sharp silhouettes of the trees. With the sun setting, our goal is to get to Tutume before dark to avoid the many animals that wander the highway at night.

By the time we reach Tutume, the town and its stores have largely gone to sleep. Our big tour group is staying at the Shumba Lodge, so we are being housed and fed by local Qalose.

Tomorrow we will pick up the healers from their villages across the Tutume district and in Francistown, Botswana’s second largest city, about two hours away. Many people in Botswana rely on more than one medical system for their health: A Western doctor for medicines and treatments, and a community healer for medicines that provide wellness, mental health, and spiritual support. Surprisingly, many people in Botswana do not think highly of this unique knowledge, even though they may use it themselves or have practicing healers in their family.

In my experience, traditional healers have spent years learning about medicinal plants and their uses. When speaking to them, they often sound like pharmacists or scientists, and they use scientific and hypothesis-driven methods to understand and improve their plants. In addition to studying these plants, we want to help validate their uniqueness. If biomedical scientists and healers can combine their respective knowledge and work together constructively, I really believe we will discover new ways to improve health and wellness that are not being considered today.

This is a typical business street in Tutume, although there are also modern strip malls and supermarkets as well.
This is the Shumba Lodge, where we had several peacock and cats as companions.

Research and Rackets

Written by The Wistar Institute on . Posted in Featured News.

For Wistar’s Pratik Bhojnagarwala, the game of squash keeps him focused on his research.

During most days of the week, you can find post-doctoral trainee Pratik Bhojnagarwala in the Weiner lab, performing research projects at the bench or scouring results to determine where his findings may lead. Or, as the Vice President of Fundraising and Partnerships for Wistar’s Trainee Association, he might be coordinating activities and events for Wistar’s training programs, helping students get the most out of their experience at Wistar.

The work can be intense, with countless hours spent reviewing data, designing experiments, or reading up on the latest papers to track findings by other scientists.

“There might be weeks after I’ve finished 10 experiments, then I need to analyze all the data. The next steps are to figure out what I need to do to move the project forward. Some days I’m heavily focused at the bench, and other days I’m at my desk analyzing data.”

But if you’re hoping to find Pratik Monday or Thursday evenings, don’t bother looking in any Wistar lab. He’ll be farther afield, focused not on cancer cells but on the path of a small, rubber ball.

He’ll be sweating it out on a squash court.

“It’s almost religious for me. I arrange my schedule trying to make sure I can play each week,” Bhojnagarwala says of his squash routine. “I have a group of people that I’ve been playing with for over 10 years at this point. It’s not just physical exercise, it’s also a social gathering. I really try and make it mandatory.”

For those in the know, Philadelphia is a squash mecca. The sport’s overseeing body, U.S. Squash, was founded in the city in 1904. Then, in 2020, the city converted an old armory on Market St, adjacent to Drexel’s campus, turning it into the Arlen Specter U.S. Squash Center, a 40,000 square foot facility that further elevated Philadelphia’s prestige in the squash world.

These days, Pratik meets up with friends at the nearby Drexel University squash courts for his weekly sessions.

Pratik’s path to squash started during graduate studies at Penn, when a few classmates invited him to join their matches. Over time he, too, picked up the sport, and it became an integral part of his weekly routine.

The court offers a much-needed respite from his day job, burning off energy and clearing his head. “I try not to miss anything that helps with my physical fitness, relaxation and gets me out of the lab,” Pratik explains. “I play with a group of people from very different walks of life — not everybody is in science. So just getting to talk to those people and learning from them — it’s a good way to disconnect. And it’s been very rewarding.”

In some ways, squash offers a parallel to what Pratik does in the lab. He might follow a path, take it wherever it leads, and then pivot based on what he finds. There’s a cadence to both, and a need to think on your feet and react to unexpected results: in squash, a strange bounce can suddenly send the ball straight at your head, while in the lab a set of results may change the trajectory of your research plan.

For Pratik, this is all part of the journey.

After receiving his master’s degree, he spent several years as a research technician at Penn before moving on to his Ph.D. work. “It was not the most traditional career path because I got into grad school later on,” he explains. “I … spent almost six years as a research technician at Penn before I had to go to grad school.”

The experience, however, is something that he values and would recommend to others. “I would definitely advise people to take a year or two after their undergrad or masters, work in a lab and … figure out if that is something they even want to do.”

In fact, Pratik recently defended his thesis and attributes that lab experience, in part, to the successful outcome. “Leading up to where I got on the stage was nerve wracking, but once I was there it felt very natural. I think it was because of the five years that spent in the lab, especially in the Wistar lab. We make full presentations during lab meetings, so it helped my confidence.”

But behind all his academic success and commitment is a simple rule: Pratik firmly believes in outside activities to clear your head and rejuvenate your soul. “It’s very important to find time … to disconnect and switch off, just go out there and do other things.”

Notes from the Field: Dr. Ian Tietjen in Africa, Part One

Written by The Wistar Institute on . Posted in Featured News.

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

3 August 2023 – Today we are in Gaborone, the capital city of Botswana in Southern Africa, to prepare for a biomedical workshop that we are planning to hold next week in Tutume. Tutume is the main town of the Tutume district in Northeast Botswana, and Dr. Khumoekae Richard, a postdoc in Dr. Luis Montaner’s lab, and I began engaging with traditional healers back in 2019. We have been interested in working in Tutume because it has a large, complex traditional medicine system in addition to the Western medical system that we are more familiar with. However, in Tutume, the medicinal plant preparations and uses to manage HIV/AIDS, COVID-19, cancer, hypertension, and other diseases, are relatively undocumented. 

We want to understand how healers identify and use local medicinal plants and how they may work at the molecular and cellular levels. Importantly, we also want to engage with the communities in a way that creates a trusting, open dialogue. For example, it is essential that we do not simply “take the medicines, make money, and never return.” Instead, we need to find new ways to work with healers over the long term so that their indigenous knowledge directly and primarily leads to local advances and benefits for both healers and their communities. We hope this workshop will be a first step toward achieving this.

Richard is originally from Botswana and grew up near Tutume, so he is fluent in the local languages (Setswana and I-Kalanga) and knows all the local customs and nuances. Since 2019, local Tutume healers have been particularly welcoming and open to working with him. From 2020-2022, Richard was fortunate to interview 13 healers from the region and document the medicinal plants they use to treat local people and their ailments. We focused on plants used for HIV, but they provided information on many others. 

Richard collected 196 plants, of which 83 were bio-authenticated by a botanist at the University of Botswana. We just published the first manuscript in June 2023 (PMID: 37301306), but now it is time to meet the healers in-person and find ways to move this collaboration forward together. 

For this visit, we showed healers and the local Tutume community some of the biomedical laboratory techniques that we typically use. We invited healers to bring plant samples to the workshop without disclosing their identities, and we will attempt to make extracts and test them for various bioactivities. We hope this workshop will help demystify scientists and hopefully jump-start new discussions of what we can do together. Richard and I are learning how to do this workshop under the guidance of Prof. Kerstin Andrae-Marobela at the University of Botswana, who has pioneered this approach in other parts of Botswana and elsewhere. We will soon be joined by researchers and knowledge-keepers from Canada and South Africa as well. 

Today Richard and I had the opportunity to meet with the Honourable Dr. Douglas Letsholathebe, the Minister of Education and Skills Development of Botswana. He was formerly a physics professor at the University of Botswana and has a keen interest in incorporating local indigenous knowledge systems into Botswana’s economy to strengthen local knowledge, education, and natural resources. He is a good ally for work like this, and we hope we can be a good ally for him. 

Richard also took us to Re Ja Sets, a traditional hut outside of Gaborone that cooks traditional Setswana food. Setswana food is simple and elegant at the same time — the traditional dish is usually beef or chicken on top of pap (milled corn), sorghum and pumpkin, or millet, with cabbage and maybe some spicy pepper sauce. Unlike most meat in the United States, Botswana’s protein has been free to spend its life running around and foraging; it also gets cooked right away. As a result, the flavor and texture are unlike anything we can get in a supermarket or restaurant in the West. The whole meal is very social: we sit in the hut and talk cordially with everyone around us, including the local farmers and restaurant owner. Everyone eats with their hands, but somehow, I seem to just make a mess instead. 

Meeting and discussing Indigenous community and healer engagement projects with the Honourable Dr. Douglas Letsholathebe, Minister of Education and Skills Development of Botswana (second from left), far left is Dr. Khumoekae Richard, second from right is Dr. Ian Tietjen, and far right is Prof. Kerstin Andrae-Marobela.

Best dinner ever! (At least so far!)

Avi Srivastava, Ph.D.

Written by The Wistar Institute on . Posted in Our Scientists.

Assistant Professor, Genome Regulation and Cell Signaling Program, Ellen and Ronald Caplan Cancer Center

Srivastava is a computational biologist interested in advancing our understanding of the interplay among cellular and molecular modalities that determines cell fate.

Srivastava completed his undergraduate studies in computer science at the College of Engineering in Roorkee, India. He went on to earn his doctoral degree in Computational Biology from Stony Brook University, New York, and he then completed a postdoctoral fellowship at the New York Genome Center and New York University.

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The Srivastava Laboratory

215-898-3700

asrivastava@wistar.org

The Srivastava Laboratory

The Srivastava lab is dedicated to the holistic understanding of how the epigenome affects the transcriptional processes that determine cell fate. During hematopoiesis, multipotent hematopoietic progenitor cells navigate a series of regulatory steps to transform into various cell lineages essential for optimal function. Given the pivotal role that disrupted epigenomic regulatory patterns play in the progression of leukemia, exploring the chromatin dynamics within both unsuccessful (malignant) hematopoietic differentiation and healthy, successful differentiation allows us to decipher their underlying molecular mechanisms.

Our lab focuses on the intricacies of blood cell development, with a special emphasis on dysregulation in leukemia. We pursue this approach with a combined methodology that includes epigenetic, computational, and cancer biology analysis. By using state-of-the-science multimodal single-cell technologies and sophisticated, uncertainty-aware computational models, the Srivastava lab dissects chromatin state dynamics and their aberrations during cell differentiation.

Staff

  • Postdoctoral Fellow

    Rajeev Ramisetti, Ph.D.

  • Research Assistant

    Calen Nichols

Available Positions

We constantly seek out individuals with expertise in multi-disciplinary fields such as mathematics, biology, computer science, and related disciplines. Positions at multiple levels, including staff scientists and postdocs for both computational and experimental research, are available. Interested candidates should send a brief statement of their research interests (1-2 pages), CV, and their reference to asrivastava@wistar.org

Research

1. FAST AND EFFICIENT METHODS FOR BULK RNA-SEQ QUANTIFICATION

The accuracy of transcript quantification using RNA-seq data depends on many factors, such as the choice of alignment or mapping method and the quantification model. The alignment of sequencing reads to a transcriptome is a common and important step in many RNA-seq analysis tasks. While the choice of quantification model is important, considerably less attention has been given to the effect of various read alignment approaches on quantification accuracy. Thus, we investigated the influence of mapping and alignment of RNA-seq reads on the accuracy of transcript quantification and designed multiple novel alignment methodologies to overcome the shortcomings of lightweight approaches without incurring the computational cost of traditional end-to-end alignment.

* He, Dongze, et al. “Alevin-fry unlocks rapid, accurate and memory-frugal quantification of single-cell RNA-seq data.” Nature Methods 19.3 (2022): 316-322.
* Srivastava A., Malik L., Sarkar H., Zakeri M., Almodaresi F., Soneson C., Love MI., Kingsford C., & Patro R. (2020) “Alignment and mapping methodology influence transcript abundance estimation.” Genome Biology. 2020 Dec;21(1):1-29.
* Srivastava A., Sarkar H., Malik L. & Patro R. (2016) “Accurate, fast and lightweight clustering of de novo transcriptomes using fragment equivalence classes.” RECOMB-seq Conference. 2016 Apr 12.
* Srivastava A., Sarkar H., Gupta N. & Patro R. (2016) “RapMap: a rapid, sensitive, and accurate tool for mapping RNA-seq reads to transcriptomes.” Bioinformatics. 2016 Jun 15;32(12):i192-200.

2. UNCERTAINTY AWARE BAYESIAN METHODS IMPROVES SCRNA-SEQ QUANTIFICATION

There has been a steady increase in the throughput of single-cell (sc)RNA-seq experiments, facilitating experimental assay of millions of cells. Droplet based scRNA-seq experiments have a large set of gene-ambiguous reads and can commonly account for a quarter of the sequenced data, which stays largely unused by quantification methods. We designed alevin, a fast end-to-end pipeline to process scRNA-seq data, performing cell barcode detection, read mapping, UMI deduplication, gene count estimation, and cell barcode whitelisting. Alevin’s approach to UMI deduplication provides an uncertainty-aware Bayesian model to account for reads that multimap between genes. This addresses the inherent bias in existing tools which discard gene-ambiguous reads and improves the accuracy of gene abundance estimates.

* Mu, Wancen, et al. “Airpart: interpretable statistical models for analyzing allelic imbalance in single-cell datasets.” Bioinformatics 38.10 (2022): 2773-2780.
* Soneson C., Srivastava A., Patro R. & Stadler MB. (2021) “Preprocessing choices affect RNA velocity results for droplet scRNA-seq data.” PLOS Computational Biology. 2021 Jan 11;17(1):e1008585.
* Srivastava A., Malik L., Smith T., Sudbery I. & Patro R. (2019) “Alevin efficiently estimates accurate gene abundances from dscRNA-seq data.” Genome biology. 2019 Dec;20(1):1-6.
* Zhu A., Srivastava A., Ibrahim JG., Patro R. & Love MI. (2019) “Nonparametric expression analysis using inferential replicate counts.” Nucleic Acids Research. 2019 Oct 10;47(18):e105.

3. COMPUTATIONAL METHODS FOR SINGLE-CELL ANALYSES

scRNA-seq data is being generated at an unprecedented pace, and the accurate estimation of gene-level abundances for each cell is a crucial first step in most scRNA-seq analyses. When pre-processing the raw scRNA-seq data to generate a count matrix, care must be taken to account for the potentially large number of multi-mapping locations per read. The sparsity of scRNA-seq data, and the strong 3’ sampling bias, make it even more challenging to disambiguate cases where there is no uniquely mapped read to any of the candidate target genes. We introduced a Bayesian framework for information sharing across cells within a sample or across multiple modalities of data to improve gene quantification estimates for scRNA-seq data.

* Hao, Yuhan, et al. “Dictionary learning for integrative, multimodal and scalable single-cell analysis.” Nature Biotechnology (2023): 1-12.
* Zhang, B.*, Srivastava A.*, Mimitou E., Stuart T., Raimondi I., Hao Y., Smibert P. & Satija R. (2021) “Characterizing cellular heterogeneity in chromatin state with scCUT\&Tag-pro.” Nature Biotechnology 40.8 (2022): 1220-1230.
* Stuart T., Srivastava A., Lareau C. & Satija R. (2021) “Single-cell chromatin state analysis with Signac.” Nature Methods (2021): 1-9.
* Srivastava A., Malik L., Sarkar H. & Patro R. (2020) “A Bayesian framework for inter-cellular information sharing improves dscRNA-seq quantification.” Bioinformatics. 2020 Jul 1;36(Supplement\_1):i292-9.

4. INTEGRATED ANALYSES OF THE EPIGENOME TO UNDERSTAND THE MOLECULAR BASIS OF HEMATOPOIETIC MALIGNANCIES

An impaired hematopoietic differentiation process underlies bone marrow malignancies like leukemia, but we still lack the mechanistic understanding of the sequence of regulatory events that misleads the differentiation process. Since epigenomic regulatory patterns are major features of leukemic development, understanding the chromatin dynamics of a failed (malignant) hematopoietic differentiation process can help define the molecular basis of leukemia. A prerequisite to such an understanding is a framework that allows investigation of the progressive changes in the activity of the regulatory elements (RE) during hematopoietic differentiation. Single-cell CUT&Tag (scCUT&Tag) technology is well-suited for such studies as RE activity through histone modification profiles can be investigated in a lineage-specific manner. Using scCUT&Tag we will investigate the RE and progressive changes in their activity during hematopoiesis. First, we will define a multimodal reference mapping framework for mouse hematopoiesis. This framework will allow us to integrate multiple histone modification profiles onto one reference and compare the chromatin states of the RE between a wild type (WT) and mouse model with loss of function in histone methyl transferase (HMT). Second, since HMTs regulate transcription through the interaction network of RE. We will define a chromatin state aware map that dynamically links REs across developmental trajectories. We will use this framework to investigate the changes in the interaction of REs due to HMT loss. Third, since the transcriptional state of a cell emerges from the underlying gene regulatory network (GRN), We will integrate single-cell gene expression data with histone modification profiles and extend it to define a chromatin state aware model of GRN. We will compare the WT and HMT loss experiments and define the differential GRN.

* Srivastava A. (2020) “Integrated analyses of the epigenome to understand the molecular basis of hematopoietic malignancies.”, Project Number: K99CA267677.

Srivastava Lab in the News

Selected Publications

  • Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro

    Zhang B, Srivastava A, Mimitou E, Stuart T, Raimondi I, Hao Y, Smibert P, Satija R. Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro. Nat Biotechnol. 2022 Aug;40(8):1220-1230. doi: 10.1038/s41587-022-01250-0. Epub 2022 Mar 24. PMID: 35332340; PMCID: PMC9378363.

  • Alevin efficiently estimates accurate gene abundances from dscRNA-seq data

    Srivastava A, Malik L, Smith T, Sudbery I, Patro R. Alevin efficiently estimates accurate gene abundances from dscRNA-seq data. Genome Biol. 2019 Mar 27;20(1):65. doi: 10.1186/s13059-019-1670-y. PMID: 30917859; PMCID: PMC6437997.

  • Alignment and mapping methodology influence transcript abundance estimation

    Srivastava A, Malik L, Sarkar H, Zakeri M, Almodaresi F, Soneson C, Love MI, Kingsford C, Patro R. Alignment and mapping methodology influence transcript abundance estimation. Genome Biol. 2020 Sep 7;21(1):239. doi: 10.1186/s13059-020-02151-8. PMID: 32894187; PMCID: PMC7487471.

  • Dictionary learning for integrative, multimodal and scalable single-cell analysis

    Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, Srivastava A, Molla G, Madad S, Fernandez-Granda C, Satija R. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2023 May 25. doi: 10.1038/s41587-023-01767-y. Epub ahead of print. PMID: 37231261.

  • Alevin-fry unlocks rapid, accurate and memory-frugal quantification of single-cell RNA-seq data

    He D, Zakeri M, Sarkar H, Soneson C, Srivastava A, Patro R. Alevin-fry unlocks rapid, accurate and memory-frugal quantification of single-cell RNA-seq data. Nat Methods. 2022 Mar;19(3):316-322. doi: 10.1038/s41592-022-01408-3. Epub 2022 Mar 11. PMID: 35277707; PMCID: PMC8933848.

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Cores Day 2023

Written by The Wistar Institute on . Posted in Events.

Special Event
Wednesday, Sep. 13, 2023

Join us during this free event and get to know the nearly 100 research core facilities representing The Wistar Institute, CHOP and UPenn.

The annual Cores Day event is a joint venture with CHOP, PSOM and The Wistar Institute, in an effort to showcase the many outstanding biomedical research resources and services available throughout our campus. This event is an opportunity for students, faculty, and staff to interface with a multitude of research core facilities via informational presentations provided by core facility personnel.

Lobby, Smilow Center for Translational Research

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2023 Champion Run for Research

Written by The Wistar Institute on . Posted in Events.

Special Event
Sunday, Nov. 12, 2023

Support the Wistar Trainee Association and their transformative research by joining us at the 2023 Champion Run for Research. This 2-mile fun run and walk starts at the Wistar facility at 3601 Spruce Street in Philadelphia and ends at the foot of the Philadelphia Art museum steps. All funds raised will directly support training, education, and the development of our next generation of biomedical researchers. Thank you for your support!

3601 Spruce Street, Philadelphia, PA 19104

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The Wistar Institute Recruits Dr. Avi Srivastava as Assistant Professor 

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA—(Sept. 7, 2023)—The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, is pleased to announce the recruitment of Avi Srivastava, Ph.D., to the Ellen and Ronald Caplan Cancer Center, where he joins Wistar’s Gene Expression and Regulation Program as an Assistant Professor.

A computational biologist, Dr. Srivastava brings expertise in advanced computational methods that can be used to establish powerful predictive research tools in cancer biology. “The opportunity to pursue my research at The Wistar Institute is invaluable,” says Dr. Srivastava. “I’m excited to launch the Srivastava Lab at an institution renowned for its unwavering dedication to cancer research.”

“We welcome Dr. Srivastava with great enthusiasm. His appointment to Wistar demonstrates our continued commitment to expanding our best-in-class research talent,” says Dario Altieri, M.D., Wistar president and CEO, director of the Ellen and Ronald Caplan Cancer Center and the Robert and Penny Fox Distinguished Professor. “Computational biology is set to play a pivotal role in the future of biomedical research, and we are delighted to have Dr. Srivastava contribute his expertise to this critical field here at Wistar.”

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The Wistar Institute, the first independent, nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a culture of biomedical collaboration and innovation. Wistar scientists are focused on solving some of the world’s most challenging and important problems in the field of cancer, infectious disease, and immunology. Wistar has been producing groundbreaking advances in world health for more than a century, consistent with its legacy of leadership in biomedical research and a track record of life-saving contributions in immunology and cell biology. wistar.org

Luis J. Montaner, D.V.M., D.Phil

Written by The Wistar Institute on . Posted in Our Scientists.

  • Executive Vice President

  • Director, HIV Cure and Viral Diseases Center

  • Herbert Kean, M.D., Family Professor

  • Associate Director for Shared Resources, Ellen and Ronald Caplan Cancer Center

  • Genome Regulation and Cell Signaling Program, Ellen and Ronald Caplan Cancer Center

  • Scientific Director, Humanized Models of Disease Facility

  • Scientific Director, Flow Cytometry Facility
  • Scientific Director, Biomedical Research Support Facility

Montaner studies the mechanisms of disease in HIV-1 infection, cancer, COVID-19, and emerging viral infections (monkeypox), exploring new strategies to boost the natural function of the immune system in order to combat viral-associated disease or cancer progression.

Montaner obtained his D.V.M., Veterinary Medicine from Kansas State University in 1989 and his D.Phil. in Experimental Pathology from University of Oxford, U.K., in 1995. He joined The Wistar Institute in 1995 as an assistant professor and was promoted to professor in 2007. Montaner was named the Herbert Kean, M.D., Family Endowed Chair Professorship in 2015.

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The Montaner Laboratory

215-898-3934

montanerlab@wistar.org

The Montaner Laboratory

At Wistar, the Montaner laboratory focuses on immune system-based research using laboratory models of virus infection, animal models of infection and/or cancer, and clinical cohort studies to provide a clinic-to-bench research program that informs new strategies to combat HIV and or cancer. The Montaner lab is also a leading center of a Martin Delaney Collaboratory focused on HIV cure-directed research (see beat-hiv.org). Patient- and animal-based collaborative studies extend from Philadelphia across the United States and Puerto Rico, Mexico, Europe, South America, Southern Africa, and Vietnam. Current research focuses on:

  • Identifying new strategies to reverse mechanisms of immunodeficiency caused by viral infection and/or cancer processes via testing new immune-enhancing strategies in patient-based studies (specimens, clinical trials), and animal models (humanized mice models, non-human primates).
  • Exploring new ways to augment HIV-1 control beyond current therapies in order to achieve durable remission and/or permanent control of infection without the need for continued antiretroviral therapy.
  • Understanding the role of targeting myeloid cells in cancer progression.
  • Determining the impact of substance use disorder therapy on immune functionality and HIV reservoir retention in opioid-dependent persons living with HIV.
  • Determining the impact of COVID-19 infection and/or vaccination on immune activation and HIV reservoirs in persons living with HIV.
  • Antiviral discovery strategies based on natural products and small molecule lead optimization.

Watch this video to learn more about HIV cure research.

Staff

  • Research Assistant Professor

    Ian Tietjen, Ph.D.

  • Senior Staff Scientists

    Livio Azzoni, M.D., Ph.D.
    Emmanouil Papasavvas, Ph.D.
    Costin Tomescu, Ph.D.
    Zhe Yuan, Ph.D.

  • Staff Scientist

    Gwendolyn Cramer, Ph.D.

  • Postdoctoral Fellows

    Avishek Bhuniya, Ph.D. <br> Khumoekae Richard, Ph.D. <br> Dmitry Zhigarev, Ph.D.

  • Research Assistants

    Maria de Grecia Cauti Mendoza
    Yong Chen
    Matthew Fair
    Adiana Ochoa Ortiz
    Emery Register
    Brian Ross
    Paridhima Sharma
    Qixun Sun
    Xiao Sun
    Guorui Zu

  • Clinical Coordinator

    Ken Lynn, R.N.

  • Clinical Research Assistant

    Bashir Fadulalmola <br> Ola Mohamed

  • BSL-2+ Laboratory Manager

    Jessicamarie Morris

  • Associate Director, HIV Program

    Beth Peterson

  • Administrative Coordinator

    Chelsea Anderson

Available Positions

Postdoctoral fellow positions are available in the Montaner laboratory, with a focus on cancer and immunotherapy system-based research through a combination of both murine-based models and human translational studies. The preferred candidate is a recent Ph.D. or equivalent with a strong background in immunology, animal models, and molecular/cellular biology. Experience with molecular screening, bioinformatics, microscopy, and flow cytometry is a plus. Individuals eligible for National Research Service Award (NRSA) funding are highly desirable. Motivated candidates are encouraged to submit their CV and references to: montanerlab@wistar.org.

Research

The Montaner lab directs several international teams and advances basic translational research focused on immunology, infectious disease, and cancer. The lab has expertise on human immunology (innate response), HIV cure-directed efforts, cancer immunotherapy, and clinical trials.

  • BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy

    In 2021, the BEAT-HIV Collaboratory received a second, five-year, $29.15 million Martin Delaney Collaboratory (MDC) award and was joined by a third principal investigator Robert  F. Siliciano, M.D., Ph.D., from Johns Hopkins University in addition to co-principal investigators Luis J. Montaner, D.V.M., D.Phil., from Wistar, and James L. Riley, Ph.D., from the University of Pennsylvania. The new award is one of 10 grants funded in 2021 by the National Institutes of Health’s (NIH) “Martin Delaney Collaboratories to Cure HIV” initiative to a highly-select group of U.S.-led teams charged with advancing global efforts to develop a cure for HIV. Building on the success of the initial award made in 2016, when the NIH granted nearly $23 million to the BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy. While the initial cycle from 2016-2021 funded the BEAT2 clinical trial, the most recent cycle of funding focuses more on basic science and did not include clinical trial support.

    The BEAT-HIV Delaney Collaboratory is a partnership of more than 85 leading HIV investigators, from academia to industry partners working with community-based organization Philadelphia FIGHT, to test combinations of several novel immunotherapies under new preclinical research. The new cycle of BEAT-HIV funding established three research goals, based on goals outlined in the NIH program announcement:

    • Understand the basic mechanisms underlying persistence of the viral reservoir during ART, what cell populations contribute to rebound after treatment interruption, and the role played by host-related factors.
    • Develop strategies to achieve durable suppression of HIV replication in the absence of ART. Capitalizing on advances in clinical research on bNAbs, BEAT-HIV researchers will test synthetic DNA technology to better deliver the genetic blueprint for the body to make different specific bNAbs simultaneously. An additional approach will be to boost natural killer and T cell responses to achieve long-term viral suppression. Eventually, the two strategies will be combined to maximize long-term control potential.
    • Develop new approaches to eradicate the HIV reservoir. Strategies to be tested include novel drugs able to reactivate latent HIV hiding in the immune cells, combined with CAR-T cell approaches designed to change a person’s killer T cells to make them able to find infected cells more efficiently. In addition, researchers will apply a technology called mRNA-LNP to make cells resistant to HIV. The ultimate goal is to identify which approaches have the best potential and test them in combination to achieve complete HIV eradication.
    BEAT-HIV2 CLINICAL STUDIES – COMPLETE

    We completed enrollment in each HIV cure-directed clinical trial funded under the BEAT-HIV umbrella from 2016-2021.

    The first study was to determine if treatment with pegylated interferon alpha 2b (peg-IFN-α2b) together with neutralizing antibodies 3BNC117+10-1074 will result in a reduction of viral rebound and reduction in the amount of latent HIV DNA in peripheral blood cells and tissues of individuals with chronic HIV infection upon an antiretroviral treatment (ART) interruption. By measuring the changes in viral rebound after ART interruption as a surrogate measure of the latent reservoir and immune control, the study will establish if this combined immunotherapy strategy should be considered as a component of future viral eradication strategies. Visit ClinicalTrials.gov under NCT03588715 for more information. Visit ClinicalTrials.gov under NCT03588715 for more information. Data analysis is underway.

    The second study tested a clinical strategy that combined two gene therapy vectors to genetically modify T cells purified from study participants using the chimeric antigen receptor (CAR) technology to make these cells highly specific in recognizing HIV-infected cells. In addition, these T cells will be made HIV-resistant by using Zinc-finger Nucleases (ZFNs) that target CCR5, an HIV entry molecule. As a result of these genetic modifications, immune cells will be rendered specific in their killing capacity while also resistant against HIV infection, which is expected to enhance their intrinsic ability to clear HIV-infected cells and result in durable viral suppression after suspension of the antiretroviral therapy. To learn more about this clinical trial, visit ClinicalTrials.gov (NCT03617198). Data analysis is underway.

    HOME-BASED VIRAL LOAD TESTING DEVICE – ENROLLMENT COMPLETE

    BEAT-HIV investigators partnered with Merck, Inc. and Tasso, Inc. to assess the reliability and acceptability of a home-based viral load testing device. The micro-blood collection device was previously tested concurrently with participants enrolled in each of the two BEAT-HIV clinical trials described above.

    HIV cure-directed clinical trials often include an analytic treatment interruption (ATI, learn more about that here). ATIs require frequent clinic visits to monitor participants’ viral load to keep it within study safety guidelines. The COVID epidemic changed the research landscape, including a stated desire among study participants and community advocates to reduce the number of study visits (and potential exposure to COVID-19 during transit and at the clinic).

    The device being tested could potentially reduce the number of required clinic visits for blood collection, but only if the home-based viral load device test works as well as standard lab-based viral load testing that can now only be done at the clinic. Just as important is to determine how people living with HIV feel about the device and the process for returning it to the lab by mail or courier, how comfortable they are with using the home-based device, and if they have any other concerns.

    The home-based viral load testing device is currently being offered by invitation to participants resuming antiretroviral therapy. At this time, the home-based viral load testing device is available within an experimental framework to determine if: 1) the device is acceptable to participants and 2) if the device provides results that are comparable to those available with traditional clinic- or lab-based viral load testing.

  • AMOHI Consortia

    OPIOIDS AND HIV: PHILADELPHIA-BASED STUDY TO DEFINE HOST FACTORS DRIVING HIV INFECTION AND IMPACTING OPTIMAL MANAGEMENT OF OPIOID USE DISORDER

    Pennsylvania is at the center of the opioid and HIV epidemic in the U.S., leading in both new HIV infections associated with persons who inject drugs (PWIDs) and in overdose deaths due to lack of optimal management of opioid drug addiction. In 2019, the federal government identified Philadelphia County as one of 48 counties responsible for >50% of new HIV diagnoses in the U.S. New infections in Philadelphia have been linked to an increase in HIV transmission from PWIDs.

    Pennsylvania also ranks fourth nationwide for deaths due to injection-drug overdose. Management of opioid addiction in persons living with HIV who are already in care for their HIV disease can be achieved by use of medications for opioid use disorder (MOUDs), including methadone, buprenorphine, or naltrexone. Even though these medications can impact immune activation on their own, what remains unknown is how the choice of methadone, buprenorphine, or naltrexone could affect the immune recovery and therefore, the future health of persons taking medications for their HIV disease and MOUD.

    The Montaner lab and collaborators in Prevention Point Philadelphia, University of Pennsylvania, and Philadelphia FIGHT are investigating the host factors driving new HIV infections in persons who inject drugs and the impact of MOUDs on immune recovery after HIV suppression by antiretroviral therapy (ART).

    PHILADELPHIA MECHANISTIC STUDY – ENROLLMENT COMPLETE

    We previously established clinical access to populations of interest in Philadelphia and  engaged  this clinical infrastructure (mobile units and multi-city clinical sites) to collect substance use/behavior (questionnaires) and biological data (blood samples) from people who inject drugs (PWIDs) who are at high risk of HIV infection, as well as PWIDs and who are living with HIV  who are taking medications for opioid use disorder. In collaboration with University of Pennsylvania, Jonathan Lax Treatment Center, the Icahn School of Medicine at Mount Sinai, and Prevention Point Philadelphia among others, we conducted a mechanistic study to determine the levels of inflammation and innate immune activation in depressed and non-depressed PWIDs, and if levels of immune activation can impact HIV susceptibility ex vivo. We will also define levels of immune activation associated with comorbidities (if elevated) in PWIDs living with HIV and who are stably suppressed under ART and taking either methadone, buprenorphine, or naltrexone to evaluate the impact of long-term opioid receptor stimulation or blockage with MOUDs on immune reconstitution in persons living with HIV. The long-term impact of this study is to investigate novel factors that can be targeted for HIV prevention in PWIDs and/or how best to manage opioid drug addiction in persons living with HIV to ensure the best immune recovery after HIV therapy able to reduce added comorbidities in the future while increasing overall survival.

    AMOHI CLINICAL TRIAL (VIETNAM)

    NIH-funded clinical trial to investigate the link between retention of chronic immune activation in HIV-1-infected opioid users receiving medication for opioid use disorder (MOUD) combined with antiretroviral therapy (ART) and starting on methadone maintenance, when compared to naltrexone or buprenorphine.

    The Montaner lab leads an international team composed of investigators from the U.S., Vietnam, and France, in collaboration with the Vietnam Ministry of Health, University of Pennsylvania, IMEA (a French-led initiative to expand access to HIV/hepatitis prevention and treatment services), the Pasteur Institute, and industry partners Alkermes, plc and Rusan. The goal of this three-arm randomized clinical trial is to evaluate the impact of long-term opioid receptor stimulation or blockage with MOUDs on immune reconstitution in people living with HIV who inject drugs and who are initiating ART. Preliminary data suggest that chronic opioid receptor engagement by an opioid receptor agonist while on ART may result in increased immune activation and inflammation associated with increased levels of persistent HIV, when compared to a full opioid receptor antagonist. To verify this hypothesis, the study will assess recovery outcomes and adherence to therapy 48 weeks after initiation of ART in 225 participants with OUD who receive either methadone (opioid receptor agonist), extended-release naltrexone (antagonist) or buprenorphine (partial agonist).

  • Coronavirus Small Molecule Drug Discovery Program

    Working with medicinal chemists and SARS-CoV-2 wildtype and variants in Wistar BSL-3 facilities, we aim to develop novel combination therapies against COVID-19 based on small molecules:

    • Small molecules that amplify the natural interferon-based host resistance already shown in early therapy trials to reverse detrimental COVID-19 disease progression. We have found small molecules that enhance the natural antiviral responses mediated by existing type I interferons without inducing further inflammation damage on their own. Once developed, this novel therapy is also expected to be applicable for use with antivirals in future viral outbreaks.
    • Small molecules that inhibit viral spread by directly blocking SARS-CoV-2 Spike protein (S) interactions with the ACE2 receptor and/or inhibiting the activity of the viral MProtease enzyme (Mpro or 3CLpro) in infected cells. We have identified small molecules that disrupt the interaction of the S protein with its human ACE2 receptor, thereby inhibiting viral entry; and small molecules that disrupt the MPro enzyme. MPro is a papain-like cysteine protease essential for processing the polyproteins that are translated from the viral RNA. Mpro can process at least 11 cleavage sites on the large polyprotein 1ab, the multifunctional protein involved in the transcription and replication of the viral RNAs. Inhibiting the activity of this enzyme would block viral replication. Because no human proteases with a similar cleavage specificity are known, such inhibitors are less likely to be toxic. We will also take advantage of the large and unique natural product and synthetic libraries available at Wistar to identify added lead molecules. We will validate identified hits using established SARS-CoV-2 Spike pseudo-virus systems as well as a live viral challenge model.

    Development of these therapeutics, to be used in combination at onset of symptoms or in those at high risk of developing symptoms, is expected to limit viral infection, preserve lung tissue integrity, and prevent progression towards a cytokine release (“storm”) syndrome associated with mortality.

  • Myeloid Cells and Cancer Progression

    Myeloid cells are critical components of the tumor microenvironment. Under physiological conditions these cells are comprised of mature terminally differentiated cells: polymorphonuclear neutrophils (PMN) and other granulocytes; macrophages (MΦ); and dendritic cells (DCs). In cancer, the myeloid compartment is dramatically affected, which is now considered one of the major immunological hallmarks of cancer. Tumor-bearing (TB) hosts accumulate immunosuppressive MΦ, DCs that are ineffective in inducing potent immune responses. The prominent change in the myeloid compartment in cancer is the expansion of pathologically activated immature myeloid cells with a potent ability to suppress immune responses — myeloid-derived suppressor cells (MDSC). In TB mice, the total population of MDSC consists of three groups of cells: pathologically activated neutrophils (PMN-MDSC) are the most abundant (>75%); pathologically activated monocytes (M-MDSC) are less abundant (<20%); and early myeloid precursors represent a small (<5%) population. The current view considers changes in myeloid cells separately, with different mechanisms applied to the different cell types. The gap in our knowledge is how these different myeloid cells can interact with each other in TB hosts. We are investigating the bridge between different populations of myeloid cells in cancer and how they orchestrate their abnormal function. The ultimate goal of this project is not only to better understand the mechanism regulating myeloid cell function in cancer, but to develop novel approaches for regulation of immune responses in cancer.

  • Development of Novel Small-molecule Rb Protein Modulator as Cancer Immunotherapy

    According to National Cancer Institute (NCI) statistics, ovarian cancer represents 1% of all cancers, and more than 19,000 women are diagnosed every year in the U.S. An estimated one woman in 87 will develop ovarian cancer during her lifetime. Although many therapeutic approaches have been tested, including surgery, radiation, chemotherapy, and immunotherapy, ovarian cancer remains extremely difficult to treat, and novel therapeutic approaches are needed. This project, funded in part by the Department of Defense, is based on therapeutic strategies that can modulate myeloid cell apoptosis resulting in an increase of anti-tumor immune responses.

  • Humanized Mouse Program: Cancer and Infectious Disease

    Absent direct clinical trials in humans, animal models of HIV infection are the best platform to explore novel pre-clinical anti-HIV strategies. Animal models for HIV infection include nonhuman primates and humanized mice. Humanized mice have emerged as a model able to be used for high-volume screening, yet the suboptimal immune differentiation that occurs has raised concern on the ability of this model to fully reflect all aspects of an immune response otherwise present in humans. The humanized mouse system has been developed to model HIV infection in humans, response to antiretroviral therapy (ART) and novel cure interventions, as well as study cancer immunotherapy in patient-derived xenograft models. A new WistarHu mice platform has been developed to support cancer immunotherapy and Wistar-based discovery of strategies against HIV based on assessing changes in viral measures on ART or effects on viral load rebound after ART interruption (Analytical Therapy Interruption, ATI). In support of this new platform, we have established ART formulations, HIV infection, HIV suppression, and characterized changes on immune reconstitution, persistent HIV measures, microbial translocation after ART and during an ATI. This platform is currently applied toward discovery and collaborative work.

  • HIV-1 Patient Partnership Program: Basic Research and HIV Social Science

    With long-standing commitment from Philadelphia FIGHT and the University of Pennsylvania along with the Robert I. Jacobs Fund of The Philadelphia Foundation, the HIV-1 Patient Partnership Program was established to provide clinical material for basic research and to sponsor the Jonathan Lax Memorial Lecture (also supported by Ken Nimblett in memory of his husband, Rusty Miller, and The Summerhill Trust, established by Martha Stengel Miller). Research with clinical material obtained from this program is focused on mechanisms of AIDS immunopathology. This collaborative link between our research team and over 6000 HIV-1 patients in the Philadelphia region led to the largest HIV Cure clinical trial to date — the BEAT-HIV Study from 2014-2018.

    The HIV-1 patient-partnership program involving participants in research is based at Philadelphia FIGHT (a community-based HIV-1 primary care provider) and Prevention Point Philadelphia. Our partnership with each community-based organization strives to develop trusted relationships and maintain meaningful, bi-directional lines of communication between investigators and communities most affected by HIV and substance use disorder. The primary objective of our community engagement strategy is to ensure communities have a clear understanding of a) the research being implemented, whether HIV-cure directed or other HIV, COVID, or monkeypox (MPOX) research, b) the stage of the research (including setting realistic expectations around HIV cure science), and c) how interested individuals can participate in and support our research agenda.

    Social Science was added to our HIV cure research agenda to enhance both our preclinical and community engagement efforts. The Social Sciences Initiative assesses the acceptability of HIV cure interventions under development and conducts empirical ethics research related to HIV cure. Working in close collaboration, BEAT-HIV investigators and community stakeholders have developed a robust agenda of educational activities, community-based projects, and basic/clinical research designed to ensure comprehensive understanding and to provide guidance on the ethical conduct of HIV cure-directed research.

    Above all, the Montaner laboratory makes its research accountable to our study participants and other stakeholders through community advisory board (CAB) review and community representation on Data Safety Monitoring Boards for clinical trials when active. In addition, we provide community-focused research presentations at Philadelphia’s AIDS Education Month, the annual Lax Lecture, and other community events, so that community members and other interested individuals are informed about the outcomes of patient-supported research.

    The Jonathan Lax Lecture honors the memory of Jonathan Lax, a businessman, inventor, teacher, and one of the best-known AIDS activists in Philadelphia’s community-based clinical research network, where he volunteered with many groups to try and speed the drug approval process. He left funds to start a clinic — today called the Jonathan Lax Center — that is now the largest provider of AIDS care in Philadelphia, independent of a patient’s ability to pay. The Lax Lecture is a public lecture held each year at The Wistar Institute, where leading international HIV scientists interact with local researchers, clinicians, and patient advocates. Previous speakers include Gates Foundation HIV Frontiers and Biotechnology Accelerator head Mike McCune, Partners in Health founder and Harvard professor Paul Farmer, Project Inform founder Martin Delaney, and 2008 Nobel Laureate Françoise Barré-Sinoussi. In 2021, the Lax Lecture celebrated its 25th year by honoring Anthony Fauci for his dedication to serving people living with HIV – the first person to receive this honor twice. The 2024 honoree is Nobel Laureate in Physiology or Medicine, Dr. Drew Weissman.

View a list of previous projects pursued by the Montaner lab.

Global Health & Partnerships

The Wistar Institute fosters a local and global community that is unified by bold scientific thinking, leadership, and a collaborative spirit. Thought leaders from nonprofits, healthcare, pharmaceutical and biotechnology companies, governments and other agencies of influence choose to work collaboratively with Wistar scientists to accelerate the creation of new therapies for patients worldwide. We have connections in locations here.

Staff

  • Research Assistant Professor

    Ian Tietjen, Ph.D.

  • Senior Staff Scientists

    Livio Azzoni, M.D., Ph.D.
    Emmanouil Papasavvas, Ph.D.
    Costin Tomescu, Ph.D.
    Zhe Yuan, Ph.D.

  • Staff Scientist

    Gwendolyn Cramer, Ph.D.

  • Postdoctoral Fellows

    Avishek Buniya, Ph.D.
    Khumoekae Richard, Ph.D.
    Dmitry Zhigarev, Ph.D.

  • Research Assistants

    Maria de Grecia Cauti Mendoza
    Yong Chen
    Matthew Fair
    Adiana Ochoa Ortiz
    Emery Register
    Brian Ross
    Paridhima Sharma
    Qixun Sun
    Xiao Sun
    Guorui Zu

  • Clinical Coordinator

    Ken Lynn, R.N.

  • Clinical Research Assistant

    Bashir Fadulalmola
    Ola Mohamed

  • BSL-2+ Laboratory Manager

    Jessicamarie Morris

  • Associate Director, HIV Program

    Beth Peterson

  • Administrative Coordinator

    Chelsea Anderson

Available Positions

Postdoctoral fellow positions are available in the Montaner laboratory, with a focus on cancer and immunotherapy system-based research through a combination of both murine-based models and human translational studies. The preferred candidate is a recent Ph.D. or equivalent with a strong background in immunology, animal models, and molecular/cellular biology. Experience with molecular screening, bioinformatics, microscopy, and flow cytometry is a plus. Individuals eligible for National Research Service Award (NRSA) funding are highly desirable. Motivated candidates are encouraged to submit their CV and references to: montanerlab@wistar.org.

Staff Highlight: Ian Tietjen, Ph.D., Focuses on Bringing Traditional Medicine into Modern Research

Ian Tietjen, Ph.D., focuses on mechanisms of viral pathogenesis, and on drug discovery and development. He uses cell biology, genetics, and high-throughput chemical screening techniques to investigate the molecular properties of HIV reservoirs in addition to influenza, coronavirus, and nipah virus.

Tietjen collaborates with local communities, medicinal plant healers, and other knowledge keepers to sustainably and ethically document and determine the bioactivities of traditional medicines used in Southern Africa, Canada, and elsewhere.

Tietjen joined Wistar as a research assistant professor in the HIV Research Program in January 2020 and he is the head of the Small Molecule Discovery and Pharmacognosy Group. He was previously an assistant professor in the Faculty of Health Sciences in Vancouver, Canada, and has worked as a group leader in Molecular and Cellular Biology at Cardiome Pharma Corp. and a senior scientist at Xenon Pharmaceuticals.

Click here to see Tietjen’s select publications.

SMALL MOLECULE DISCOVERY AND PHARMACOGNOSY GROUP

The Small Molecule Discovery and Pharmacognosy Group works with researchers, traditional healers, and other knowledge keepers who are interested in identifying and elucidating the molecular and biomedical properties of naturally produced chemical compounds and medicinal plants. The group primarily focuses on potential therapies for HIV, coronaviruses, influenza, and other infectious pathogens but also supports studies for cancer, metabolic diseases, and other illnesses. We provide assay development, laboratory training and instruction, and community engagement expertise to meaningfully work with local and Indigenous communities with traditional medicinal knowledge.

Individuals interested in working with the Small Molecule Discovery and Pharmacognosy Group can contact Ian Tietjen for more information at itietjen@wistar.org.

The mission of the BEAT-HIV Collaboratory is the define the most effective way to combine immunotherapy regimens to cure HIV.

Learn more about BEAT-HIV

Interview with Dr. Luis Montaner

The inaugural episode of The Wistar Institute’s podcast takes a deep dive with Dr. Luis Montaner, one of Wistar’s longest-serving scientists, as he discusses his lab’s groundbreaking HIV cure research and how he decided to dedicate his life to the cause of searching for an HIV cure. 

Lab Events and Photos

2016 Staff Lunch

Montaner Lab in the News

Selected Publications

  • Intact HIV reservoir estimated by the intact proviral DNA assay correlates with levels of total and integrated DNA in the blood during suppressive antiretroviral therapy.

    Papasavvas, E., Azzoni, L, Ross, B.N., Fair, M, Yuan, Z., Gyampoh, K., Sciorillo, A.C., Paggliuzza, A., Lada, S., Wu, Gioxin, G., Goh, S.L., Banck-Teets, C., Holder, D.J., Zuck, P.D., Damra, M., Lynn, K.M., Tebas, P., Mounzer, K., Kostman, J.R., Abdel-Mohsen, M., Richman, D., Chomont, N., Howell, B.J., Montaner, L.J.  2021. “Intact HIV reservoir estimated by the intact proviral DNA assay correlates with levels of total and integrated DNA in the blood during suppressive antiretroviral therapy.”  Clin. Infect. Dis. 72(3): 495-498. DOI: 10.1093/cid/ciaa809. PMID: 33527127.

  • Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH

    Tomescu, C., Kroll, K, Colon, K., Papasavvas, E., Frank, I., Tebas, P., Mounzer, K., Reeves, R.K., Montaner, L.J. 2021. “Identification of the Predominant NK Effector Subsets Mediating ADCC Against HIV-infected Targets Coated with BNAbs or Plasma from PLWH.” Eur J Immunol. 51(8): 2051-2061. DOI: 10.1002/eji.202149188. PMID: 34086344.

  • The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9

    Tietjen, I., Schonhofer, C., Sciorillo, A., Naidu, M.E., Haq, Z., Kannan, T., Kossenkov, A.V., Rivera-Ortiz, J., Mounzer, K., Hart, C., Gyampoh, K., Yuan. Z., Beattie, K.D., Rali, T., Shuda McGuire, K., Davis, R.A., Montaner, L.J. 2023. “The natural stilbenoid (-)-hopeaphenol inhibits HIV transcription by targeting both PKC- and NK-kappaB-signaling and cyclin-dependent kinase 9.” Antimicrobial Agents and Chemotherapy. 67(4): e01600-22. DOI: 10.1128/aac.01600-22. PMID: 36975214.

  • Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons

    Tebas, P., Lynn, K.M., Azzoni, L., Cocchella, G., Papasavvas, E., Fair, M., Reeves, J.D., Petropoulos, C., Lalley-Chareczko, L., Kostman, J.R., Short, W.R., Mounzer, K., Montaner, L.J. 2023. “Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons.” AIDS. DOI: 10.1097/QAD.0000000000003575.  PMID: 37070542.

  • Community engagement group model in basic and biomedical research: lessons learned from the BEAT-HIV Delaney Collaboratory towards an HIV-1 cure

    Dubé, K., Peterson, B., Jones, N.L., Onorato, A., Carter, W.B., Dannaway, C., Johnson, S., Hayes, R., Hill, M., Maddox, R., Riley, J.L., Shull, J., Metzger, D., Montaner, L.J. 2023. “Community Engagement Group Model in Basic and Biomedical Research: Lessons Learned from the BEAT-HIV Delaney Collaboratory Towards an HIV-1 Cure.” Research Involvement & Engagement 2023; 9(39): 1 – 17.  9(1): 39. DOI: 10.1186/s40900-023-00449-y. PMID 37291622.

View Additional Publications

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