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Sunita K. Agarwal, Ph.D.

Sunita Agarwal.
Scientific Focus Areas: Cancer Biology, Cell Biology, Chromosome Biology, Genetics and Genomics, Molecular Biology and Biochemistry

Professional Experience

  • Staff Scientist, NIDDK, NIH, 1999-2008
  • Postdoctoral Fellow, NIDDK, NIH, 1995-1999
  • Postdoctoral Fellow, University of Delaware, 1992-1995
  • Visiting Fellow, University of Delaware, 1991-1992
  • Ph.D., Bombay University, 1991
  • M.Sc., Bombay University, 1985

Research Goal

The general goal of our research is to identify factors that control endocrine tumorigenesis, with a focus on abnormal growth of the insulin-secreting pancreatic β-cells and the parathyroids. Investigating the molecular and genetic mechanisms of tumorigenesis will not only provide insights into the pathways of tumor syndromes, but it could also define novel pathways and processes involved in normal cell growth regulation.

Current Research

We study the molecular and genetic basis of endocrine tumorigenesis, particularly tumors of the parathyroid glands and pancreatic neuroendocrine tumors of the islet β-cells, to understand how gene regulatory events contribute to endocrine cell transformation.

Endocrine tumors develop due to abnormal cell proliferation and function of hormone-producing cells. These tumors can occur sporadically or within familial tumor syndromes such as multiple endocrine neoplasia type 1 (MEN1), a disease characterized by germline-inactivating mutations in the MEN1 tumor-suppressor gene that encodes menin. These mutations predispose to tumors of the parathyroids, anterior pituitary, and enteropancreatic neuroendocrine tissues. Also, somatic inactivation of one or both copies of the MEN1 gene is observed in 20 to 30 percent of sporadic (non-hereditary) parathyroid tumors, and in 30 to 40 percent of sporadic pancreatic neuroendocrine tumors. Studies in mouse models have demonstrated that Men1 homozygous-null mice are embryonic-lethal, and heterozygous mice show tumors similar to those found in the human MEN1 syndrome. However, how menin loss initiates tumors in specific endocrine organs is not completely understood. Thus, it is important to study tumor pathogenesis from menin loss.

Menin is a 610-amino acid nuclear protein that interacts with a variety of factors involved in transcriptional regulation, such as transcription factors and histone-modifying protein complexes. However, how the loss of menin in these interactions affects growth-related processes of specific endocrine cells has not been clearly determined. We propose that studying menin-regulated processes will help uncover the factors responsible for tumors that arise even without MEN1 gene mutation. Therefore, we are using menin as a model to identify regulatory factors that operate downstream of menin and that could be independently responsible for initiating endocrine tumorigenesis.

Applying our Research

Understanding the abnormal regulation of basic molecular processes that cause increased cell proliferation in endocrine tumors will facilitate the development of better therapeutic options for controlling endocrine tumor development. Knowledge of factors regulating cell proliferation and function in β-cell tumors will also impact the development of methods for maintaining normal β-cell mass in conditions of β-cell loss, such as in diabetes.

Need for Further Study

The genetics and pathogenesis of sporadic endocrine tumors, particularly tumors of the pituitary, parathyroid, and pancreatic neuroendocrine tissues without MEN1 gene inactivation, require further study. Researchers also need to examine whether processes perturbed upon MEN1 gene loss could point to novel mechanisms of tumorigenesis and how menin loss initiates tumors in specific endocrine organs.

Select Publications

Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.
Fahrmann JF, Wasylishen AR, Pieterman CRC, Irajizad E, Vykoukal J, Wu R, Dennison JB, Peterson CB, Zhao H, Do KA, Halperin DM, Agarwal SK, Blau JE, Jha S, Rivero JD, Nilubol N, Walter MF, Welch JM, Weinstein LS, Vriens MR, van Leeuwaarde RS, van Treijen MJC, Valk GD, Perrier ND, Hanash SM, Katayama H.
J Clin Endocrinol Metab (2023 Nov 17) 108:3260-3271. Abstract/Full Text
A Knock-In Mouse Model of the Gcm2 Variant p.Y392S Develops Normal Parathyroid Glands.
Parekh VI, Brinster LR, Guan B, Simonds WF, Weinstein LS, Agarwal SK.
J Endocr Soc (2023 Oct 9) 7:bvad126. Abstract/Full Text
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Research in Plain Language

We conduct basic research to determine the underlying cellular and molecular mechanisms responsible for normal and neoplastic growth and function of the hormone-secreting endocrine cells of the parathyroid glands, anterior pituitary, and pancreatic islets.

Last Reviewed November 2023