Research Endeavors

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Type 1 Diabetes

The Wang lab studies novel approaches that can prevent and treat type 1 diabetes using state-of-the-art therapeutic approaches with or without islet transplantation.

 

Islet cell transplantation is a promising therapy for patients with type 1 diabetes. However, there are two major problems with this treatment. First, there are not enough islets available for transplantation. Second, islets after transplantation are often injured during islet harvest and have compromised function. Furthermore, rejection of islets is a problem that needs to be addressed. Ongoing projects in the Wang lab focus on solving these problems, and major areas of investigation include:

  • The roles of a protective anti-inflammatory agent called alpha-1 antitrypsin.

  • Using mesenchymal stromal cells for the treatment of type 1 diabetes with or without islet transplantation.

  • Developing novel methods to prevent or treat rejection of transplanted cells.

  • Determine if stem cells can restore function to the pancreas.

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Chronic Pancreatitis (CP)

Chronic pancreatitis alters the normal structure and function of the pancreas. Current therapies for CP patients focus on medical or surgical pain relief. Future therapies hope to restore function and relieve pain by novel methods. These include: 

  • Total pancreatectomy with islet autotransplantation (TP-IAT)

  • Stem cell therapy

  • Islet transplantation options without surgery

Together with Drs. David B Adams and Katherine A Morgan, we are developing interventional procedures including induction of protective genes, nano-encapsulation, and co-transplantation with mesenchymal stem cells to improve islet yield quantity and quality in order to prevent onset of surgical diabetes after TP-IAT in patients with chronic pancreatitis.

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Generation of Insulin-Producing
β-Cells using iPSCs

Generation of insulin-producing pancreatic β-cells and islet organoids from inducible pluripotent stem cells (iPSCs) promises to provide unlimited cell sources for β-cell replacement therapy. Human iPSCs can be induced into glucose-responsive insulin-secreting cells in vitro, and transplantation of these cells ameliorates hyperglycemia in diabetic mice. However, the glucose-stimulated insulin-secreting capacity of most iPSC-derived beta cells is still low compared with endogenous islets, suggesting the need to improve the cell differentiation procedure to promote β-cell differentiation and maturation.

Our projects focus on:

  • Studying the molecular basis of β-cell development and maturation.

  • Producing fibroblasts or peripheral blood mononuclear cell (PBMC)-derived human iPSCs and differentiating them into pancreatic β-cells.

  • Exploring the role of the endoplasmic reticulum chaperon, the glucose-regulated protein 94 (GRP94), and the mitochondria protein, uncoupling protein 2 (UCP-2), in β-cell development and function using iPSC as a vector.