Brinda Alagesan
Education:
B.A. University of Pennsylvania (2009)
MD/PhD Stony Brook University (2020)
Advisor: David Tuveson, MD-PhD
Cold Spring Harbor Laboratory
Graduate Program:Genetics
Research Interest:
Nearly all cases of human pancreatic ductal adenocarcinoma (PDAC) are characterized by activating mutations in the KRAS oncogene. Previous studies using xenograft and genetically engineered mouse models of PDAC, as well as 2-dimensional cultured cell lines, have identified a number of changes in cell metabolism that occur as a result of Kras mutation. These studies have been hampered by the inability to study tumor cells in comparison to “normal” pancreas cells in vivo. Using a novel 3-dimensional culture system, pancreatic organoids can be isolated from mice bearing normal, pre-neoplastic and neoplastic pancreata, cultured and genetically manipulated ex vivo, and transplanted back into syngeneic wildtype mice. I am using the organoid model system to study mitophagy and changes in metabolism that occur during PDAC progression in a Kras-dependent manner and to determine how these changes contribute to tumorigenesis and tumor maintenance in vivo.
Awards:
NCI F30 NRSA
Publications:
(MSTP-supported publications indicated with an *)Miyabayashi K, Baker LA, Deschênes A, Traub B, Caligiuri G, Plenker D, Alagesan B, Belleau P, Li S, Kendall J, Jang GH, Kawaguchi RK, Somerville TDD, Tiriac H, Hwang CI, Burkhart RA, Roberts NJ, Wood LD, Hruban
RH, Gillis J, Krasnitz A, Vakoc CR, Wigler M, Notta F, Gallinger S, Park Y, Tuveson DA. Intraductal Transplantation Models of Human Pancreatic Ductal Adenocarcinoma Reveal Progressive Transition of Molecular Subtypes.Cancer Discov. 2020 Oct;10(10):1566-1589. doi: 10.1158/2159-8290.CD-20-0133. Epub 2020 Jul 23. PMID: 32703770*Humpton, T.J.#, Alagesan, B.#, …, Tuveson, D. A. (2019.) Oncogenic Kras induces Nix-mediated mitophagy to promote pancreatic cancer. Cancer Discovery, in press. # contributed equally
* Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., . . . Tuveson, D. A. (2019). The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. Science, 364(6446), 1156-1162
* Boj, S. F., Hwang, C. I., Baker, L. A., Chio, II, Engle, D. D., Corbo, V., Jager, M.,…, Alagesan, B., … Clevers, H. and Tuveson, D. A. (2015). Organoid models of human and mouse ductal pancreatic cancer. Cell, 160(1-2), 324-338.
Alagesan, B. #, Contino, G. #, Guimaraes, A. R., Corcoran, R. B., Deshpande, V., Wojtkiewicz, G. R., . . . Bardeesy, N. (2015). Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer. Clin Cancer Res, 21(2), 396-404. # contributed equally
Hezel, A. F., Deshpande, V., Zimmerman, S. M., Contino, G., Alagesan, B., O'Dell, M. R., . . . Bardeesy, N. (2012). TGF-beta and alphavbeta6 integrin act in a common pathway to suppress pancreatic cancer progression. Cancer Res, 72(18), 4840-4845.
Yu, M., Ting, D. T., Stott, S. L., Wittner, B. S., Ozsolak, F., Paul, S., Ciciliano, J. C., Smas, M. E., Winokur, D., Gilman, A. J., Ulman, M. J., Xega, K., Contino, G., Alagesan, B., Brannigan, B. W., Milos, P. M., Ryan, D. P., Sequist, L. V., Bardeesy, N., Ramaswamy, S., Toner, M., Maheswaran, S. and Haber, D. A. (2012). RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature, 487(7408), 510-513.
Garza, L. A., Liu, Y., Yang, Z., Alagesan, B., Lawson, J. A., Norberg, S. M., . . . Cotsarelis, G. (2012). Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med, 4(126), 126-134.
Gurumurthy, S.# Xie, S. Z.#, Alagesan, B., Kim, J., Yusuf, R. Z., Saez, B., . . . Bardeesy, N. (2010). The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature, 468(7324), 659-663. # contributed equally
