The Xiao Lab for Diabetes Research

Developing a Better Understanding of Diabetes, Immunology, and Disease Interactions

Produced by pancreatic beta cells, insulin is a key regulator of glucose homeostasis. Insufficient insulin leads to diabetes mellitus, a metabolic disease that affects over 300 million people worldwide. As beta cell replacement can be an efficient therapy for all types of diabetes, Principal Investigator Xiangwei Xiao, MD, PhD, and his research team are exploring the mechanisms that govern beta cell regeneration at both cellular level and molecular level in search of new therapies to prevent and treat diabetes.

Diabetes includes the two most common kinds, type 1 (T1D) and type 2 (T2D), as well as some uncommon types, including chronic pancreatitis-related diabetes (CPRD) and type 3 diabetes (T3D), which has been linked to losses in cognitive function.

The most prevalent form of diabetes, T2D, is believed to result from the loss of sensitivity of other cells to insulin. It is often associated with insulin resistance, inadequate insulin production and secretion by the pancreatic beta cells, beta cell dysfunction, and eventual beta cell loss. Believed to result from autoimmune destruction of the insulin-producing beta cells in the pancreas, T1D is usually diagnosed in children and young adults. While it is accompanied by more severe symptoms and complications than T2D, it constitutes only about 5% of all diabetes cases.

The lab team has found that pancreatic macrophages play a pivotal role in the initiation and progression of diabetes, and it is now dissecting the precise molecular interaction between macrophages and beta cells. Xiao Lab researchers are also trying to develop practical treatments of various diabetes through manipulating macrophages in vivo.

Crosstalk Between Beta Cells and Macrophages

Macrophages mediate the response of beta cells to metabolic needs and inflammatory insults.

Macrophages mediate the response of beta cells to metabolic needs and inflammatory insults.

Areas of Focus

The ultimate goals of the Xiao Lab are to prevent the occurrence of diabetes and to develop effective treatments for all kinds of diabetes, using state-of-the-art cell biology and molecular biology tools.

Researchers have five primary areas of focus:

  • Generation of new beta cells, through manipulation of the interplay among different signaling pathways that govern the beta cell replication.
  • Protection of beta cell identity and prevention of loss of functional beta cells during disease-associated stress or aging.
  • Understanding the crosstalk between beta cells and other cell types, such as endothelial cells and macrophages, which play a pivotal role in regulation of beta cell function and homeostasis.
  • Understanding the interaction among different diseases through systemic immunological adaption (for example, type 1 diabetes, asthma, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis).
  • Studying diabetes-associated aging, or Alzheimer’s disease.

Lab Team & Contact Information

Xiangwei Xiao, MD, PhD

Principal Investigator
xiangwei.xiao@chp.edu
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Yinan Jiang, MD, PhD
Research Assistant
yinan.jiang12@chp.edu

Chaoban Wang, MD
Visiting Scholar
chaoban.wang11@chp.edu

Jieqi Qian, MD
Visiting Scholar
skyler_qian@163.com

Contact Us

The Xiao Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, 6th floor, Bay 9
4401 Penn Avenue
Pittsburgh, PA 15224
412-692-7519

Activities

Presentations at Scientific Meetings

2019

Yinan Jiang, MD, PhD, gave a platform presentation, entitled “Placental Growth Factor in Mouse Beta Cells Plays an Essential Role in Gestational Beta Cell Growth,” at the Midwest Islet Club Annual Meeting in Ann Arbor, Michigan.

2017

Xiangwei Xiao, MD, PhD, was a speaker at the American Diabetes Association Annual Meeting in San Diego.

2016

Xiangwei Xiao, MD, PhD, was an invited symposium speaker at the American Diabetes Association Annual Meeting in New Orleans.

Publications

Placental Growth Factor in Beta-cellsplays an Essential Role in Gestational Beta-cell Growth
Yang W, Jiang Y, Wang Y, Zhang T, Liu Q, Wang C, Swisher G, Wu N, Chao C, Prasadan K, Gittes GK and Xiao X
BMJ Open Diabetes Research & Care
2020 Jan

Calpastatin Mediates Development of Alzheimer’s Disease in Diabetes
Zhu L, Gong L, Yang T, Xiao X
Journal of Alzheimers Disease
2019 Mar 19

Prion Protein is Essential for Diabetic Retinopathy-associated Neovascularization
Zhu L, Xu J, Liu Y, Gong T, Liu J, Huang Q, Fischbach S, Zou W, Xiao X
Angiogenesis
2018 May 30

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

SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes
Xiao X, Fischbach S, Zhang T, Chen C, Sheng Q, Zimmerman R, Patnaik S, Fusco J, Ming Y, Guo P, Shiota C, Prasadan K, Gangopadhyay N, Husain SZ, Dong H, Gittes GK
Diabetes
2017 Oct

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

Pancreatic Duct Cells as a Source of VEGF in Mice
Xiao X, Prasadan K, Guo P, El-Gohary Y, Wiersch J, Gaffar I, Shiota C, Gittes GK
Diabetologia
2014 Feb 18

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

TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload-Induced β-Cell Proliferation
Xiao X, Wiersch J, El-Gohary Y, Guo P, Prasadan K, Paredes J, Welsh C, Shiota C, Gittes GK
Diabetes
2013 Apr

Opportunities to Join

We’d Like to Hear From You!

The Xiao Lab is looking for talented graduate and undergraduate students who are interested in joining the team for part-time research. If you are interested, please contact Dr. Xiangwei Xiao via email.