Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Defining epigenetic underpinnings of neuroendocrine lineage carcinomas

Award Number: K99CA312809
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

Group Awards By:

View Award Description

Defining epigenetic underpinnings of neuroendocrine lineage carcinomas - Abstract Phenotypic plasticity is a hallmark of cancer wherein cancer cells can undergo a lineage transformation to evade therapeutic pressure. Cancer lineage plasticity is facilitated by epigenetic changes in chromatin profiles. Up to 15% of prostate cancers develop treatment resistance by transforming from conventional prostate adenocarcinoma (PRAD) to small-cell neuroendocrine prostate cancer (NEPC), a process marked by epigenetic dysregulation. Polycomb repressive complex 2 (Polycomb) is critical for formation and maintenance of facultative heterochromatin for gene silencing and cell-fate specification. Over four years of postdoctoral research in Dr. Himisha Beltran’s lab, I defined the differential activity of Polycomb in PRAD compared to NEPC and identified key genes that are de-repressed driving NEPC lineage reprogramming. My extensive epigenetic profiling of clinical samples and models revealed long facultative heterochromatin regions at key NE-related genes in PRAD, potentially representing insulated Polycomb domains. The transformation of these domains into euchromatin and their role in NEPC lineage plasticity remain unexplored. Understanding Polycomb domains' functional role in NEPC progression could advance our knowledge of cancer lineage plasticity and lead to novel therapeutic strategies. Additionally, the roles of Polycomb domains, chromatin remodelers, and shared epigenetic features in other neuroendocrine cancers remain under studied. The central hypothesis is that Polycomb domains and their modulators drive neuroendocrine lineage carcinoma. I will use genetic perturbation studies in clinically relevant cell line and organoid models, along with integrative epigenetic and transcriptomic analyses, to test this hypothesis through three specific aims: (1) to determine the functional role of Polycomb domains in mediating NEPC lineage plasticity; (2) to define the role of Polycomb regulating factors in NEPC progression; (3) to determine critical epigenetic regulators of neuroendocrine carcinomas. The results will pave the way for development of targeted therapies for neuroendocrine cancers. In addition to my primary mentor, Dr. Beltran, a world leader in NEPC biology and clinical management, my K99 Advisory Committee includes esteemed experts: Dr. Myles Brown, specializing in epigenetics in hormone- dependent cancers; Dr. Matthew Oser, focusing on the epigenetics of small cell lung cancer; Dr. James DeCaprio, a leader in neuroendocrine tumor biology; Dr. Ramesh Shivdasani, an expert in epigenetics and gastrointestinal neuroendocrine carcinoma biology; and Dr. Srinivas Viswanathan, a GU clinican-scientist and accomplished Associate Professor recently transitioning to independence. Collectively, they have mentored over 200 successful trainees worldwide. With their guidance, I will achieve the training objectives set for the K99 phase, emerging as an expert in epigenetic mechanisms mediating neuroendocrine lineage cancers. The K99/R00 award will empower me to pursue the best research and career development opportunities, facilitating a successful transition to independence and enabling me to launch an ambitious research program.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $170,394 )
2026	2026	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Research Manpower	000	1	6/30/2026	NEW	$170,394
														Subtotal = $170,394

Grand Total All Awards = $170,394

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining epigenetic underpinnings of neuroendocrine lineage carcinomas

Award Number: K99CA312809

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer