Pamela Itkin-Ansari's Research Focus
Pamela Itkin-Ansari's Research Report
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.
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.
We also study the signaling pathways involved in:
- beta-cell differentiation
- beta-cell function
- beta-cell replication and regeneration
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
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
Itkin-Ansari P, Levine F
Cell Biochem Biophys 2004 ;40(3 Suppl):103-12
Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role For Peroxiredoxin 4 in Proinsulin Folding.
Tran DT, Pottekat A, Mir SA, Loguercio S, Jang I, Campos AR, Scully KM, Lahmy R, Liu M, Arvan P, Balch WE, Kaufman RJ, Itkin-Ansari P
Diabetes 2020 May 26 ;
Role of Proinsulin Self-Association in Mutant <i>INS</i> Gene-Induced Diabetes of Youth.
Sun J, Xiong Y, Li X, Haataja L, Chen W, Mir SA, Lv L, Madley R, Larkin D, Anjum A, Dhayalan B, Rege N, Wickramasinghe NP, Weiss MA, Itkin-Ansari P, Kaufman RJ, Ostrov DA, Arvan P, Liu M
Diabetes 2020 May ;69(5):954-964
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