Specializing In:Tumor microenvironment, Tumor metabolism, Kras and cMyc signaling, Pancreatic cancer
Special Interests:Cytokine biology, Oncogene addiction, T cells
About Prasenjit Dey
Dr. Prasenjit Dey joined the faculty of Immunology at the Roswell Park Comprehensive Cancer Center in August 2019 as an Assistant Professor of Oncology/Immunology. Prasen earned his MS in Clinical Chemistry at Manipal University, India and a PhD in Biochemistry in the laboratory of Dr. Jan-Ake Gustafsson at University of Houston, TX. During his graduate studies, he was one of the first to identify FOXO3a as transcriptionally regulated by estrogen receptor (ER) beta. Decreased expression of ERbeta in prostate cancer leads to downregulation of FOXO3a resulting in increased proliferation (Dey, et al. Oncogene, 2014). He further demonstrated that ERbeta splice variants have opposite roles in prostate cancer (Dey, et al. Molecular Endocrinology, 2012) and also showed that ERbeta2, a splice variant interacts with HIF1alpha for its oncogenic function (Dey, et al. PlosOne, 2015).
Dr. Dey conducted his postdoctoral fellowship in Dr. Ronald DePinho’s laboratory at the University of Texas MD Anderson Cancer Center in Houston, TX. Here he identified a specific vulnerability in a sub-set of pancreatic cancer patients where malic enzyme 2 is homozygously co-deleted along with the tumor suppressor gene SMAD4 (Dey, et al. Nature, 2017). He then continued his research on the theme of precision medicine and has co-authored a paper on mutual exclusivity of CHD1 and PTEN in prostate cancer (Zhao, et al., Nature, 2017). He along with others has demonstrated that Yap1 mediated regulation of MDSC in prostate cancer (Wang et al. Cancer Discovery, 2016). He also co-authored a paper on Kras regulation of tumor microenvironment in colorectal cancer (Liao et al. Cancer Cell, 2019) and a paper on novel function of p53 in SMARCB1 deficient tumors (Carugo et al. Cancer Cell, 2019). At the same time, he co-authored a comprehensive review on the genetics and biology of pancreatic cancer (Ying, et al. Genes and Development, 2016).
Dr. Dey’s laboratory has specific research interest in elucidating novel therapeutic strategies that involves metabolic and cytokine pathway targets with a goal to identify alternative therapeutic strategies to target hard to treat cancers. His broad research interests include tumor metabolism, cytokine biology, and immuno-metabolism. Dr. Dey’s laboratory is funded by grants from the National Cancer Institute (NCI). Additionally, Dr. Dey has received numerous awards and honors that include a Department of Defense (DoD) Postdoctoral Fellowship.
Roswell Park Comprehensive Cancer Center
- Associate Professor of Oncology
- Department of Immunology
Jacobs School Of Medicine And Biomedical Sciences, State University of New York at Buffalo
- Associate Professor
Education and Training:
- 2013 - PhD - Biochemistry, University of Houston, Houston, TX
- Postdoctoral Fellowship, Cancer Biology, UT MD Anderson Cancer Center, Houston, TX
- 2012 - The Endocrine Society
- 2010 - American Association for Cancer Research (AACR)
- 2009 - Sponsored member, American Association for the Advancement of Science (AAAS)
Honors & Awards:
- 2018 - NCI Pathway to Independence Award (K99/R00)
- 2018 - CSCO Young Investigator Travel Award, Chinese Society of Clinical Oncology
- 2018 - AACR-Aflac, Inc. Scholar-in-Training Award, The American Association for Cancer Research
- 2017 - The Harold C. and Mary L. Daily Endowed Fellowship Award, UT MD Anderson Cancer Center, TX
- 2014 - US Department of Defense (DOD) Postdoctoral Fellowship
The tumor microenvironment remains a challenging area of research, because of the large number of actors such as myofibroblasts (MF), extracellular matrix (ECM), and immune cells interacting in a dynamic fashion with the cancer cells that determines the overall outcome. Our research is primarily focused on understanding how tumor microenvironment factors such as cytokines and chemokines synergize with tumor intrinsic oncogenic pathways for tumor initiation and survival.
Role of CD4+ T cells in pancreatic cancer progression.
A hallmark feature of PDAC is an extensive desmoplastic stroma comprised of myofibroblasts (MF), extracellular matrix (ECM), and immune cells. Among the infiltrating immune cells, the study is mainly focused on cytotoxic T cells, NK cells and M1 macrophages in inhibiting tumor initiation and progression. Less explored is the potential role of the immune cells, which are early responders to the mutation events in PDAC, especially CD4+ T cell in disease promotion. CD4+ T helper cells, with its multiple subtypes (TH 1, 2, 9, 10, 17, 22) are critical for inflammatory processes in cancer. Among them, TH2 subtypes can promote tumor growth via various mechanisms that include induction of M2 macrophage polarization.
Recently, we have identified a unique role of TH2 polarized CD4 T-cells in collaborating with oncogenic Kras in transforming indolent PanIN into malignant pancreatic tumor. Our data show an important role of tumor infiltrating TH2 cells and its prototypic cytokines IL4 and IL13 driving tumor initiation and progression. Concurrently, oncogenic Kras upregulates the expression of cytokine receptors IL2rg, IL4ra and IL13ra1 that, upon IL4 and IL13 engagement, activates the Jak1-Stat6 pathway. The goal of this project is to identify factors that are released by cancer cells that attract TH2 cells into the tumor microenvironment and if blocking of TH2 infiltration mediated pathway has any therapeutic benefit.
Cytokine mediated metabolic reprogramming in cancer.
A major component of tumor microenvironment is the secreted factors arising from infiltrating immune cells, stroma and cancer cells itself, which shapes the overall trajectory of the disease. Transcriptomic analysis has identified cMyc upregulation upon treatment with IL4 or IL13. In agreement with cMyc roles in influencing tumor metabolism, targeted metabolomic analysis have shown an increase in glycolysis upon treatment with IL4 or IL13. In consistence with increase in glycolysis upon IL4 or IL13 treatment, there is an increase in expression of glycolytic enzymes (Hexokinase II, lactate dehydrogenase and pyruvate dehydrogenase). This data is especially intriguing because prior in vitro studies failed to capture the dependence of cancer cells on glycolysis, probably because of the absence of these vital cytokines in vitro culture media forcing the cancer cells to utilize glutamine as carbon source. The goal of this project is to investigate the role of IL4 and/or IL13 in driving an alternative metabolic circuit especially the acceleration of glycolytic pathways. We will determine whether cMyc mediated metabolic shift is essential for cancer cell survival. We will use biochemical and metabolic techniques to understand whether cMyc increases the glucose consumption which contributes to cancer cell biomass leading to aggressive tumor growth.
- Prasenjit Dey, Jun Li, Jianhua Zhang, Surendra Chaurasiya, Anders Strom, Huamin Wang, Wen-Ting Liao, Frederick Cavallaro, Parker Denz, Vincent Bernard, Er-Yen Yen, Giannicola Genovese, Pat Gulhati, Jielin Liu, Deepavali Chakravarti, Pingna Deng, Tingxin Zhang, Federica Carbone, Qing Chang, Haoqiang Ying, Xiaoying Shang, Denise J. Spring, Bidyut Ghosh, Nagireddy Putluri, Anirban Maitra, Y. Alan Wang and Ronald A. DePinho. Oncogenic Kras driven metabolic reprogramming in pancreas cancer cells utilizes cytokines from the tumor microenvironment. Cancer Discovery. Online February 11, 2020, doi: 10.1158/2159-8290.CD-19-0297
- Liao WT, Boutin A, Dey P, Wang G, Zhao D, Lan Z, Li J, Li J, Shang X, Tang M, Jiang S, Ma X, Chen P, Katkhuda R, Korphaisarn K, Chang A, Overman MJ, Spring DJ, Maeda DY, Zebala JA, Zhang J, Maru DM, Kopetz S, Wang YA, and DePinho RA. KRAS-IRF2 axis drives immune suppression and immune therapy resistance in colorectal cancer. Cancer Cell 2019 March doi.org/10.1016/j.ccell.2019.02.008.
- Genovese G, Carugo A, Tepper J, Robinson FS, Li L, Svelto M, Nezi L, Corti D, Minelli R, Pettazzoni P, Gutschner T, Wu CC, Seth S, Akdemir KC, Leo E, Amin S, Molin MD, Ying H, Kwong LN, Colla S, Takahashi K, Ghosh P, Giuliani V, Muller F, Dey P, Jiang S, Garvey J, Liu CG, Zhang J, Heffernan TP, Toniatti C, Fleming JB, Goggins MG, Wood LD, Sgambato A, Agaimy A, Maitra A, Roberts CW, Wang H, Viale A, DePinho RA, Draetta GF, Chin L. Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer. Nature 542(7641): 362-366 (2017) doi: 10.1038/nature21064.
- Zhao D, Lu X, Wang G, Lan Z, Liao W, Li J, Liang X, Chen JR, Shah S, Shang X, Tang M, Deng P, Dey P, Chakravarti D, Chen P, Spring DJ, Navone NM, Troncoso P, Zhang J, Wang YA, DePinho RA. Synthetic essentiality of chromatin remodeling factor CHD1 in PTEN deficient cancer. Nature 542: 484-488 (2017) doi:10.1038/nature21357.
- Dey P, Baddour J, Muller F, Wu CC, Wang H, Liao WT, Lan Z, Chen A, Gutschner T, Kang Y, Fleming J, Satani N, Zhao D, Achreja A, Yang L, Lee J, Chang E, Genovese G, Viale A, Ying H, Draetta G, Maitra A, Wang YA, Nagrath D, DePinho RA. Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature 542: 119–123 (2017) doi:10.1038/nature21052.
- Wang G, Lu X, Dey P#, Deng P, Wu CC, Jiang S, Fang Z, Zhao K, Konaparthi R, Hua S, Zhang J, Li-Ning-Tapia EM, Kapoor A, Wu CJ, Patel NB, Guo Z, Ramamoorthy V, Tieu TN, Heffernan T, Zhao D, Shang X, Khadka S, Hou P, Hu B, Jin EJ, Yao W, Pan X, Ding Z, Shi Y, Li L, Chang Q, Troncoso P, Logothetis CJ, McArthur MJ, Chin L, Wang YA, DePinho RA. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discovery 6(1): 80–95 (2016) doi: 10.1158/2159-8290.CD-15-0224.