Our Science

Dario C. Altieri, M.D.

Dario C. Altieri, M.D.

  • Director, The Wistar Institute Cancer Center
  • Executive Vice President
  • Chief Scientific Officer
  • Robert and Penny Fox Distinguished Professor
  • 215-495-6975, Office
Summary

The Altieri laboratory explores the mechanisms that underlie how tumor cells survive and proliferate in cancer. In particular, his laboratory is interested in how tumor cells evade the normal processes that cause cells with genetic faults to self-destruct. Understanding these mechanisms could provide new therapeutic targets and novel approaches for virtually every type of human cancer. 

Born in Milan, Italy, and educated at the University of Milan School of Medicine, Dario C. Altieri, M.D., became a practicing clinician at the University, where he would later earn a postgraduate specialty degree in clinical and experimental hematology. In 1987, he joined the Scripps Clinic and Research Foundation in La Jolla, California, first as a research fellow and later as a member of the faculty.

In 1994, Dr. Altieri became an associate professor at the Yale University School of Medicine, was named professor in 1999, and served in that role until 2002 when he was recruited as the founding chair of the Department of Cancer Biology at the University of Massachusetts Medical School.

In 2005, he co-founded both the national Cancer Biology Training Consortium, which promotes scientific excellence in the next generation of cancer researchers; and the Pancreatic Cancer Alliance, an all-volunteer patient advocacy organization devoted to supporting pancreatic cancer research and education.

Dr. Altieri joined the Institute as the Wistar Cancer Center Director and its first Chief Scientific Officer in September 2010.  In addition to his leadership role, Dr. Altieri leads an active investigation program, studying the functional implications of a family of genes, known as Inhibitors of Apoptosis (IAP), which are essential for proliferation and survival of cells. In particular, Dr. Altieri has demonstrated that at least one IAP gene, called survivin, is required for both functions, and has been shown to be over-produced in virtually every human cancer.
 
Dr. Altieri and his team are currently focused on understanding the biology of survivin and how exploiting this biology may provide new cancer therapies. 

A second research theme being actively pursued in the Altieri laboratory focuses on mechanisms of cellular adaptation by tumor cells, and how these processes promote resistance to treatment and acquisition of a more malignant phenotype. Current efforts focus on elucidating the role of molecular chaperones compartmentalized in mitochondria in regulating tumor bioenergetics, adaptation to cellular stress and cell survival

Selected Publications

1    Chae, Y. C., Angelin, A., Lisanti, S., Kossenkow, A. A., Speicher, K. D., Wang, H., Powers, J. F., Tischler, A. S., Pacak, K., Fliedner, S., Michalek, R. D., Karoly, E. D., Wallace, D. C., Languino, L. R., Speicher, D. W. and Altieri, D. C. (2013) Landscape of the mitochondrial Hsp90 metabolome in tumors.  Nature Commun. 4:2139.

2    Caino, M. C., Chae, Y. C., Vaira, V., Ferrero, S., Nosotti, M., Martin, N. M., Weeraratna, A., O’Connell, M., Jernigan, D., Fatatis, A., Languino, L. R., Bosari, S., and Altieri, D. C. (2013) Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer
cells.  J. Clin. Invest. 123:2907-2920.

3    Chae, Y. C., Caino, M. C., Lisanti, S., Ghosh, J. C., Dohi, T., Danial, N. N., Villanueva, J., Ferrero, S., Vaira, V., Santambrogio, L., Bosari, S., Languino, L. R., Herlyn, M., and Altieri, D. C. (2012) Control of tumor bioenergetics and survival stress signaling by mitochondrial Hsp90s.  Cancer Cell 22:331-344.  PMCID: PMC3615709

4    Siegelin, M. D., Dohi, T., Raskett, C. M., Orlowsky, G. M., Powers, C. M., Gilbert, C. A., Ross, A. H., Plescia, J., and Altieri, D. C. (2011) Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells.  J. Clin. Invest.  121:1349-1360.

5    Mehrotra, S., Languino, L. R., Raskett, C. M., Mercurio, A. M., Dohi, T., and Altieri, D. C. (2010) IAP regulation of metastasis.  Cancer Cell. 17:53-64.

6    Kang, B. H., Siegelin, M. D, Plescia, J., Raskett, C. M, Garlick, D. S., Dohi, T., Lian, J. B., Stein, G. S., Languino, L. R., and Altieri, D. C. (2010) Preclinical characterization of mitochondrial-targeted small molecule Hsp90 inhibitors, Gamitrinibs, in advanced prostate cancer.  Clin. Cancer Res. 16:4779-4788.  PMCID: PMC2948625.

7    Kang, B. H., Plescia, J., Song, H. Y., Meli, M., Colombo, G., Beebe, K., Scroggins, B., Neckers, L., and Altieri, D. C. (2009) Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90.  J. Clin. Invest. 119:454-464
Altieri, D. C. (2008) Survivin, cancer networks and pathway-directed drug discovery.  Nature Rev. Cancer 8:61-70.

8    Kang, B. H., Plescia, J., Dohi, T., Rosa, J., Doxsey, S. J., and Altieri, D. C. (2007) Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network.  Cell. 131:257-270.

9    Dohi, T., Xia, F., and Altieri, D. C. (2007) Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection.  Mol. Cell. 27:17-28.