The laboratory of José Conejo-Garcia is primarily focused on understanding how certain white blood cells are co-opted by ovarian tumors in order to aid in their survival. These “vascular leukocytes,” defined by Conejo-Garcia and his colleagues in 2005, both stimulate growth of blood vessels while also serving a role in regulating the immune system. Vascular leukocytes, therefore, help feed tumors while telling the immune system to tolerate the presence of the tumor. However, under the right set of activating signals, the same cells can be transformed to drive anti-tumor immunity.

Conejo-Garcia and his team are devising strategies to create new therapies that will utilize patients’ own immune systems to elicit protective anti-tumor immunity against—and prevent recurrence of—ovarian cancer.

Born and educated in Spain, Conejo-Garcia received his medical degree from the University of Zaragoza in 1990. After completing a residency in Clinical Chemistry at the University Hospital of Guadalajara, he began to work toward a Ph.D. in Molecular Oncology at the University of Alcala. In 1998, Conejo-Garcia began post-doctoral work at the University of Bern in Switzerland, where he delved deeper into the study of tumor biology.

After two years working in a biotechnological company in Germany, Conejo-Garcia took a second post-doctoral fellowship in 2001, this time at the University of Pennsylvania, where he applied his interest in tumor biology to the study of ovarian cancer. It was then he began to focus on the tumor microenvironment, the collection of neighboring, healthy cells that nourish the tumor and enable it to thrive. It is a theme that he carried with him to Dartmouth Medical School, where he became an assistant professor in 2005.

Conejo-Garcia’s current research explores the biology of a subset of immune cells known as dendritic cells, which are co-opted by ovarian tumors to protect them from the immune system as a whole, rather than boosting protective immune responses. His laboratory has discovered that eliminating these immune cells from the tumor microenvironment kills ovarian tumor cells and may slow aggressive forms of the cancer.

Conejo-Garcia’s laboratory program explores an innovative approach to fighting ovarian cancer by exploiting the tumor’s reliance on its “microenvironment,” the collection of neighboring, healthy cells that nourish the tumor and enable it to thrive. In particular, he has developed a “Trojan Horse” method that reprograms white blood cells within the microenvironment—which otherwise have the effect of preventing the spontaneous anti-tumor activity of the immune system—so that they activate immune cells to attack the ovarian tumor.

1 - Wasiuk A, Dalton DK, Schpero WL, Stan RV, Conejo-Garcia JR, Noelle RJ. Mast cells impair the development of protective anti-tumor immunity. Cancer Immunol Immunother. In Press.

2 - Deng Z, Wang Z, Xiang C, Molczan A, Baubet V, Conejo-Garcia J, Xu X, Lieberman X, Dahmane N (2012). Formation of Telomeric Repeat-Containing RNA (TERRA) Foci in Highly Proliferating Mouse Cerebellar Neuronal Progenitors and Medulloblastoma. J Cell Sci. In Press.

3 - Tchou J, Wang LC, Selven B, Zhang H, Conejo-Garcia J,  Borghaei H, Vondeheide RH, Albelda SM, June CH, Zhang PJ. Mesothelin, a novel immunotherapy target for triple negative breast cancer. Breast Cancer Res Treat. In Press.

4 - Cubillos-Ruiz JR, Baird J, Rutkowski M, Scarlett UK, Camposeco-Jacobs AL, Anadon-Arnillas J, Harwood N, Korc M, Fiering S, Sempere L, Conejo-Garcia JR (2012). Reprogramming tumor-associated dendritic cells in vivo using microRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res., 72: 1683-1693.

5 - Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, Baird J, Cubillos-Ruiz JR, Jacobs AC, Gonzalez J, Weaver J, Fiering S, Conejo-Garcia JR (2012). Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J. Exp. Med., 209: 495-506.

6 - Cubillos-Ruiz J.R., Martinez D., Scarlett U.K., Rutkowski M.R., Nesbeth Y.C., Camposeco-Jacobs A.L., Conejo-Garcia J.R. (2010) CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells. Oncotarget, 1: 329-338.

7 - Sempere LF, Preis M., Yezefski T., Ouyang H., Suriawinata A.A., Silahtaroglu A., Conejo-Garcia J.R., Kauppinen S., Wells W., Korc M. (2010) Fluorescence-based co-detection with protein markers reveals distinct cellular 2 compartments for altered microRNA expression in solid tumors. Clin. Cancer Res., 16: 4246-55.

8 - Nesbeth Y, Martinez D, Toraya S, Scarlett U,  Cubillos-Ruiz J,  Rutkowski M, Conejo-Garcia J. (2010) CD4⁺ T cells elicit host immune responses to MHC-II- ovarian cancer through CD40-mediated licensing of dendritic cells and CCL5 secretion. J. Immunol., 184: 5654-62.

9 - Robinson R.T., Khader S.A., Martino C.A., Fountain J.J., Teixeira-Coelho M., Pearl J.E., Smiley S.T., Winslow G.M., Woodland D., Walter M.J., Conejo-Garcia J.R., Gubler U. & Cooper A.M (2010). Mycobacterium tuberculosis infection induces IL12Rb1 splicing 1 to generate a novel IL12Rβ1 isoform that enhances DC migration. J. Exp. Med., 207:591-605.

10 - Scarlett UK, Cubillos-Ruiz JR, Nesbeth YC_, Martinez DG, Engle X_, Ahonen CL, Conejo-Garcia JR. (2009) In situ stimulation of CD40 and Toll-like receptor 3 transforms ovarian cancer-infiltrating dendritic cells from immunosuppressive to immunostimulatory cells. Cancer Res.; 69: 7329–37.

11 - Cubillos-Ruiz J., Engle X., Scarlett U., Martinez D., Barber A., Elgueta R., Wang L., Nesbeth Y., Durant Y., Gewirtz A.T., Sentman C.L., Kedl R., Conejo-Garcia JR (2009). Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity. J. Clin. Invest.; 119: 2231-44.

12 - Nesbeth Y, Scarlett U, Cubillos-Ruiz J, Martinez D,  Engle X, Turk, MJ, Conejo-Garcia JR (2009) Elimination of ovarian cancer dendritic cells boosts endogenous anti-tumor immunity elicited by adoptively transferred lymphocytes. Cancer Res.; 69: 6331-6338.

13 - Huarte E, Cubillos-Ruiz J, Nesbeth Y, Scarlett U, Martinez D, Buckanovich RJ, Benencia F, Stan R, Keler T, Sarobe P, Sentman CL, Conejo-Garcia JR. (2008) Depletion of dendritic cells delays ovarian cancer progression by boosting anti-tumor immunity. Cancer Res.; 68: 7684-91.

14 - Huarte E, Cubillos-Ruiz J, Nesbeth Y, Scarlett U, Martinez D, Pioli P, Rigby W, Guyre P, Conejo-Garcia, JR. (2008) PILAR is a novel modulator of human T cell expansion. Blood; 112: 1259-68.