The Gittes Lab for Diabetes and Pancreatitis Research

Endogenous Alpha-to-Beta Cell Trans-differentiation Procedure for the Treatment of Type 1 Diabetes

Type 1 diabetes is characterized by a loss of insulin-producing beta cells in the pancreas. Due to lack of sufficient available islet for transplantation, there has been an ongoing interest to identify the alternate source of beta cells for replacement therapy.

New evidence shows that differentiated endocrine cells have significant plasticity and can trans-differentiate into functional beta cells. Our lab has developed a viral-mediated gene therapy protocol to reverse type 1 diabetes in mouse models through alpha-to-beta cell conversion in vivo. We also found that the new beta cells derived from alpha cells not only reduced blood glucose in the type 1 diabetic mouse model but also appear to be protected against an immune attack in non-obese diabetic (NOD) mice for a significant amount of time. Currently, we are attempting similar strategies in non-human primates as a precursor to human clinical trials.

Intra-ductal Intervention Strategy for Chronic Pancreatitis

Chronic pancreatitis is a common problem affecting both young and adult. If not treated, it can lead to severe complications and eventually diabetes or pancreatic cancer. The current treatment is pancreas resection or total pancreatectomy, followed by autologous pancreatic islet transplantation. We are developing an intra-ductal intervention strategy to chemically ablate inflamed ductal and exocrine tissue while preserving the islet tissue. Our tests on rodents and non-human primates suggest this is a viable alternative to surgery; in both species, we saw significant improvement in pain management, and the animals maintained normal blood glucose without insulin treatment.

George Gittes, MD

Principal Investigator
gittesgk@upmc.edu
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Krishna Prasadan, PhD
Senior Research Scientist and Lab Manager
Director of Rangos Cell Imaging Core
krishna.prasadan@chp.edu

Mohamed Saleh, MD
Research Scientist and Assistant Professor of Pediatric Endocrinology
mohamed.saleh@chp.edu

Anuradha Sehrawat, PhD
Research Scientist
sehrawata@upmc.edu

Tina Zhang, PhD
Research Scientist
ting.zhang4@upmc.edu

Yang Wan, PhD
Post-doctoral Fellow
yan.wang18@chp.edu

Guy Agostinelli
Technician
agostinelligm2@upmc.edu

Jeremy Friedman
Technician
jeremy.friedman@chp.edu

Thomas Madison
Technician
madison.thomas7@chp.edu

Ranjeet Kalsi, DO
Visiting Scholar and Surgical Resident (PGY3) / Research Fellow
kalsirs@upmc.edu

Nada Mohamed, MD
Visiting Scholar
nada.mohamed2@chp.edu

Kartikeya Sharma, MD
Visiting Scholar
sharmak4@upmc.edu

Ali Abdelhafiz, MD
Visiting Scholar
ali.abdelhafiz@chp.edu

Contact Us

The Gittes Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, 6th Floor
4401 Penn Avenue
Pittsburgh, PA 15224
412-692-7291

View current news below featuring the research, staff and advancements of the Gittes Lab for Diabetes and Pancreatitis Research at UPMC Children’s Hospital of Pittsburgh’s Richard King Mellon Institute for Pediatric Research. Please check back often for continued updates.

In the News

UPMC Children’s and Pitt Researcher Receives $2.59 Million NIH Grant for Diabetes Gene Therapy
UPMC Children’s Hospital Press Release (7/21/20)  

Gene Therapy Restores Normal Blood Glucose Levels in Mice With Type 1 Diabetes
EurekAlert! (1/4/2018)

Alpha to Beta Cell Reprogramming: Stepping toward a New Treatment for Diabetes
Cell Stem Cell (1/4/2018)

Gene Therapy Reverses Autoimmune Diabetes in Mice
UPMC Children’s Hospital Press Release (1/4/2018)

National Institutes of Health Research Grants

Multi-year Research Project Grants (R01) from the National Institutes of Health are helping to drive the innovative investigations being conducted by the Gittes Lab.

Endogenous Alpha-to-beta Cell Transdifferentiation in Diabetes
R01 DK112836 (Gittes)
04/01/2017 – 03/31/2022

Mapping Disease Pathways for Biliary Atresia
R01 DK109365-01A1 (Sindhi)
04/01/2017 – 03/31/2022

Alpha Cells Conversion to Beta Cells in Non-human Primates
R01 DK120377 (Gittes)
09/30/2018 – 08/31/2020

EGF and TGF-β Signaling Synergy in β-cell Proliferation
R01 DK111460 (Gittes)
09/10/2016 – 08/31/2019

Evidence of a Developmental Origin of Beta-cell Heterogeneity Using a Dual Lineage Tracing Technology
Chen C, Shiota C, Agostinelli G, Ridley D, Jiang Y, Ma J, Prasadan K, Xiao X, Gittes GK
Development
2019 Jun 5

Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes
Xiao X, Guo P, Shiota C, Zhang T, Coudriet GM, Fischbach S, Prasadan K, Fusco J, Ramachandran S, Witkowski P, Piganelli JD, Gittes GK
Cell Stem Cell
2018 Jan 6

Pancreatic Cell Tracing, Lineage Tagging and Targeted Genetic Manipulations in Multiple Cell Types Using Pancreatic Ductal Infusion of Adeno-associated Viral Vectors and/or Cell-tagging Dyes
Xiao X, Guo P, Prasadan K, Shiota C, Peirish L, Fischbach S, Song Z, Gaffar I, Wiersch J, El-Gohary Y, Husain SZ, Gittes GK
Nature Protocols
2014 Oct 31

M2 Macrophages Promote Beta-cell Proliferation by Up-regulation of SMAD7
Xiao X, Gaffar I, Guo P, Wiersch J, Fischbach S, Peirish L, Song Z, El-Gohary Y, Prasadan K, Shiota C, Gittes GK
Proceedings of the National Academy of Sciences of the USA
2014 Mar 19

No Evidence for Beta Cell Neogenesis in Murine Adult Pancreas
Xiao X, Chen Z, Shiota C, Prasadan K, Guo P, El-Gohary Y, Paredes J, Welsh C, Wiersch J, Gittes GK
The Journal of Clinical Investigation
2013 Apr 27

Developmental Biology of the Pancreas: A Comprehensive Review
Gittes GK
Dev Biol
2008 Nov 18

Lineage-specific Morphogenesis in the Developing Pancreas: Role of Mesenchymal Factors
Gittes GK, Galante PE, Hanahan D, Rutter WJ, Debase HT
Development
1996 Feb 1

Onset of Cell-specific Gene Expression in the Developing Mouse Pancreas
Gittes GK, Rutter WJ
Proceedings of the National Academy of Sciences of the USA
1992 Feb 1

We’d Like to Hear From You!

The Gittes Lab is looking for talented post-doctoral fellows and graduate students interested in Diabetes research. Please contact Dr. Gittes via email if you are interested.