Pamela Itkin-Ansari, Ph.D.

Pamela Itkin-Ansari's Research Focus

Cancer, Diabetes - General, Gastric Cancer, Monogenic Diabetes, Pancreatic Cancer, Type 1 Diabetes, Type 2 Diabetes
Dr. Itkin-Ansari’s research is directed toward understanding diseases of the human pancreas. She has studied the signaling pathways controlling growth and differentiation in the pancreas in order to elucidate mechanisms leading to pancreatic pathogenesis. The lab is developing a cell based therapy for diabetes that will not require immunosuppression. New research in the lab has identified a signaling pathway controlling pancreatic cancer cell growth that is yielding new potential targets for drug discovery for pancreatic cancer.

Pamela Itkin-Ansari's Research Report

Diabetes
Genetic engineering in human pancreatic cells
Genetic engineering in human pancreatic cells

In Type I, juvenile diabetes, the insulin producing beta-cells in pancreatic islets are destroyed by the immune system and patients require exogenous insulin. In Type II diabetes beta-cells are also lost or dysfunctional and therefore, 25 percent of patients with Type II diabetes also take insulin. Unfortunately, current insulin therapy is not sufficient to prevent serious medical consequences of this disease. Islet transplantation into the liver has been evaluated as a diabetes therapy in adults. However, it is considered too risky for children because transplant patients must take potent drugs to suppress the immune system for the rest of their lives.
 

Human pancreas development
Human pancreas development

The goal of our lab is to develop a human islet transplantation therapy for children that does not require immunosuppression and is minimally invasive. Previously we determined that a durable encapsulation device protected mouse islets from immune rejection in a mouse model of Type I diabetes. The encapsulated cells were controlled diabetes in the animals. In a preclinical trial we demonstrated that the device is also immunoprotective in primates. Recently we have collaborated with a local biotech company ViaCyte in a CIRM funded study to encapsulate human embryonic stem cell derived pancreas cells. Together we demonstrated that the cells differentiate into fully functional islets inside the device and cure diabetes in mice. Remarkably, the cells functioned well even when the device was transplanted just under the skin, making the procedure minimally invasive.
 

Islet clusters in the developing pancreas
Islet clusters in the developing pancreas

We also study the signaling pathways involved in:

  • beta-cell differentiation
  • beta-cell function
  • beta-cell replication and regeneration

 

Pancreatic Cancer
Id3 (green) in human pancreatic cancer
Id3 (green) in human pancreatic cancer

We are interested in identifying the master regulators of growth control in pancreatic ductal adenocarcinoma (PDA). We found that the transcriptional repressor Id3 is profoundly upregulated in human PDA. To investigate whether Id3 might play an early role in aberrant pancreatic duct cell growth, we expressed the gene in primary human duct cells that are not normally growing. Indeed, Id3 expression was sufficient to trigger cell cycle entry. Further, the lab demonstrated that Id3 is required for pancreatic cancer cell growth. We are now studying Id3 interacting genes in order to identify optimal targets for drug discovery efforts for PDA.

Pamela Itkin-Ansari's Bio

Pamela Itkin-Ansari earned her Ph.D. in Biomedical Sciences from the University of California San Diego, in 1999. She received postdoctoral training focused on juvenile diabetes at that same organization. In 2003, Dr. Itkin-Ansari was appointed Assistant Professor in the Department of Pediatrics and maintains UCSD as her primary affiliation. Dr. Itkin-Ansari was appointed to Sanford Burnham Prebys Medical Discovery Institute as an Adjunct Assistant Professor in 2005 and her laboratory is at SBP.
 

Other Appointments

UCSD
Sanford School of Medicine, South Dakota
 

Funding Awards and Collaborative Grants

Juvenile Diabetes Research Foundation (JDRF)
California Institute for Regenerative Medicine (CIRM)
The Hartwell Foundation
The Hirshberg Foundation
 

Honors and Recognition

2012: Invited Speaker, (International) Islet Society, Stockholm, Sweden
2012-current: Editorial Board -Islets
2012-current: Diabetes, Islets, PlosOne, Molecular Therapy- manuscript review
2012-current: Wellcome Trust-grant review
2012: Invited Speaker, Hirshberg Symposium – Pancreatic Cancer
2011: Invited Speaker, American Society of Gene and Cell Therapy, Seattle, Washington
2011: Editorial Board – World Journal of Diabetes
2011: Invited Speaker, UCLA
2011-current: Diabetelogia – manuscript review
2011-current: Editorial Board – World Journal of Diabetes
2010: Invited Speaker, 3rd International Conference on Advanced Technologies & Treatments for Diabetes, Switzerland
2010: Editorial Board -Stem Cell Reviews and Reports [SCRR]
2010: Invited Speaker, American Society of Gene and Cell Therapy, Washington, D.C
2010-current: Hartwell Foundation Biomedical Research Awardee
2010: Invited Speaker, Pancreatic Cancer Research Group, UCLA
2010-current: Faculty Advisor, SDSU CIRM Bridges Program
2009: Invited Speaker, Vanderbilt University, Nashville, Tennessee
2009: Invited Speaker, UK Consulate Stem Cell Meeting
2009: Finalist-NIH President’s New Innovator Award
2009-current: Advances in Experimental Biology and Medicine – manuscript review
2008: Health Hero Award, JDRF and Combined Health Agencies of San Diego
2008-current: Pancreas – manuscript reviewer
2008-current: JDRF – grant reviewer
2007-current: Stem Cells – manuscript reviewer
 

Other Affiliations

2012-current: Islet Society
2010-current: ASGCT
2008-current: Board of Directors, JDRF San Diego chapter
2008-2013: JDRF board of directors, San Diego
2007-current: American Association for Cancer Research
2007-current: American Diabetes Association
2007-current: American Pediatric Society/Society for Pediatric Research
2006-current: AAAS


DAR Accessory

Publications

HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter.

Kiselyuk A, Lee SH, Farber-Katz S, Zhang M, Athavankar S, Cohen T, Pinkerton AB, Ye M, Bushway P, Richardson AD, Hostetler HA, Rodriguez-Lee M, Huang L, Spangler B, Smith L, Higginbotham J, Cashman J, Freeze H, Itkin-Ansari P, Dawson MI, Schroeder F, Cang Y, Mercola M, Levine F

Chem Biol 2012 Jul 27 ;19(7):806-18

Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen.

Kiselyuk A, Farber-Katz S, Cohen T, Lee SH, Geron I, Azimi B, Heynen-Genel S, Singer O, Price J, Mercola M, Itkin-Ansari P, Levine F

J Biomol Screen 2010 Jul ;15(6):663-70

Sources of beta-cells for human cell-based therapies for diabetes.

Itkin-Ansari P, Levine F

Cell Biochem Biophys 2004 ;40(3 Suppl):103-12

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Proinsulin misfolding is an early event in the progression to type 2 diabetes.

Arunagiri A, Haataja L, Pottekat A, Pamenan F, Kim S, Zeltser LM, Paton AW, Paton JC, Tsai B, Itkin-Ansari P, Kaufman RJ, Liu M, Arvan P

Elife 2019 Jun 11 ;8

E47 Governs the MYC-CDKN1B/p27<sup>KIP1</sup>-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16<sup>INK4A</sup> and Wild-Type p53.

Scully KM, Lahmy R, Signaevskaia L, Sasik R, Medal R, Kim H, French R, James B, Wu Y, Lowy AM, Itkin-Ansari P

Cell Mol Gastroenterol Hepatol 2018 ;6(2):181-198

Induced PTF1a expression in pancreatic ductal adenocarcinoma cells activates acinar gene networks, reduces tumorigenic properties, and sensitizes cells to gemcitabine treatment.

Jakubison BL, Schweickert PG, Moser SE, Yang Y, Gao H, Scully K, Itkin-Ansari P, Liu Y, Konieczny SF

Mol Oncol 2018 Jun ;12(7):1104-1124

A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer.

Villarino N, Signaevskaia L, van Niekerk J, Medal R, Kim H, Lahmy R, Scully K, Pinkerton A, Kim S, Lowy A, Itkin-Ansari P

Oncotarget 2017 Aug 8 ;8(32):53154-53167

When Less Is Better: ER Stress and Beta Cell Proliferation.

Yong J, Itkin-Ansari P, Kaufman RJ

Dev Cell 2016 Jan 11 ;36(1):4-6

The IRE1α/XBP1s Pathway Is Essential for the Glucose Response and Protection of β Cells.

Hassler JR, Scheuner DL, Wang S, Han J, Kodali VK, Li P, Nguyen J, George JS, Davis C, Wu SP, Bai Y, Sartor M, Cavalcoli J, Malhi H, Baudouin G, Zhang Y, Yates JR III, Itkin-Ansari P, Volkmann N, Kaufman RJ

PLoS Biol 2015 Oct ;13(10):e1002277

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