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Wang Laboratory

Location

TBRC 3885 (Office)
TBRC 3698 and 3645 (Lab)

General Interests

Cancer biology, stem cell biology, regenerative medicine, systems biology, glycobiology, experimental therapeutics

View Principal Investigator Bio
Video: The 3D structure of a cerebral organoid developed in Wang Lab.

Research Areas

The self-renewal and tremendous differentiation capacity of human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), hold a great promise for the development of novel therapy and the success of regenerative medicine.

Our group leverages an integrated approach of stem cell, cancer, and systems biology to comprehensively investigate the biology, pathology, and clinical utility of hPSCs and their differentiated derivatives.

We are using hiPSC-based models to recapitulate oncogenic processes for studying the dysregulation and heterogeneity of cell signaling involved in melanoma formation. We are also highly interested in understanding how protein glycosylation is involved in the regulatory mechanisms of cellular pluripotency, neurodevelopment and the pathogenesis of human disease.

The long-term goal of our research is to provide new insights and opportunities in regenerative medicine and targeted therapy for better managing disease, including cancer and rare genetic disorders.

Wang Lab Research Areas 1
Wang Lab Research | hiPSC colonies and schematic illustration of hPSC derivation and differentiation
Top: hiPSC colonies cultured on non-proliferative feeder cells. Bottom: The schematic illustration of hPSC derivation and differentiation

Ongoing Research Programs

A research focus in the Wang lab is translational medicine aiming to understand the molecular basis of therapeutic responses in melanoma and to develop better strategies for managing patients. Besides, they have long-standing expertise and interests to study how glycoenzymes are involved in the regulation of stem cell differentiation and the developmental abnormalities in patients with congenital glycosylation/deglycosylation disorders. The active research directions in the group include:

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Targeting protein glycosylation/deglycosylation as an Achilles' heel in human cancer cells

It is known that cell signaling mediated by protein glycosylation is critically involved in cell differentiation and normal development. Interestingly, many glycosylation features in cells are significantly altered during pathogenesis like cancer formation, indicating that certain glycosylation or deglycosylation mechanisms could be highly demanded by cancer cells to sustain their viability or oncogenic signaling. Therefore, the dysregulated glycosylation represents a potentially vulnerable point in cancer cells for the identification of novel therapeutic targets with the opportunity for a broad therapeutic window. We are actively investigating multiple glycoenzymes and testing their roles in the formation and progression of cancer, including melanoma and glioblastoma. We believe this study will reveal intriguing biology and address multiple challenges in cancer therapy by understanding protein glycosylation/deglycosylation as a potential Achilles' heel of cancer.

Functional significance of glycosidase NGLY1 in neural differentiation and human cerebral development

As an enzyme that removes N-glycans from glycopeptides, N-glycanase 1 (NGLY1) deglycosylates denatured glycoproteins and enables proteasome-mediated protein degradation to efficiently occur. The mutations of the human NGLY1 gene that lead to NGLY1 deficiency have been recently identified as the cause of a previously undiagnosed congenital disorder. NGLY1-deficient patients often present with developmental delay accompanied by many neurological symptoms in the central nervous system. How the malfunction of NGLY1 causes these neurodevelopment-related abnormalities in the human brain remains unclear, forming a major obstacle for the development of potential therapeutic or protective approaches. Using an integrative approach based on human pluripotent stem cell (hPSC), cerebral organoid, and systems biology techniques, we are studying the cellular and molecular features during neurodevelopment in the absence of NGLY1 expression.

Using reprogramming approaches to model melanoma and dissect malignancy signaling

Advanced melanoma is highly metastatic and refractory to many therapeutic approaches. Although targeted therapies (e.g., a BRAF inhibitor) and immune checkpoint blockers (e.g., a monoclonal CTLA-4 antibody) have shown encouraging anticancer activity for treating patients with advanced melanoma, the tumor regression responses induced by these therapeutic agents are frequently unsustainable for the long term or are limited in a small subpopulation of patients. This suggests that there are resistance mechanisms in the cells hindering the anticancer effect and that identifying these mechanisms will be tremendously helpful for designing strategies to improve the therapeutic efficacy. Emerging evidence has shown that melanoma cells may develop resistance to these targeted therapies and further increase dependence on hyperactive MAPK signaling, partially due to the enhanced expression of the mutant BRAF protein. With expertise in cancer, stem cell, and systems biology, we work to elucidate the causes and effects of melanocytic cells developing their dependence on the MAPK signaling in the context of melanocyte development modeled using hPSCs.

Functional significance of protein glycosylation in pluripotency regulation

Much progress has been made toward understanding the regulation of cellular pluripotency in hPSCs at the molecular level and how to translate that knowledge into regenerative medicine. However, studies of protein expression and posttranslational modifications (PTMs) in hPSCs have lagged behind the genomic studies. Our group has previously identified several types of protein glycomodifications and glycan-binding proteins that are preferentially associated with the pluripotent state in hPSCs. We hypothesize that the glycoproteins with pluripotency-associated glycomodifications in hPSCs are functionally important for the regulation of cellular pluripotency. We are using proteomics and protein biochemistry approaches to delineate the roles of protein glycosylation in the regulation of pluripotency and potentially discover novel targets for manipulating pluripotency in cells for regenerative medicine and other biomedical applications. Currently, we are focusing on protein fucosylation and sialylation.

Current Members

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Jiangnan (Johnnie) Hu, MD, MS, DPhil

Postdoctoral Fellow

PhD, Neuropharmacology, University of North Texas Health Science Center; MS, Neurosurgery & Neuroscience, Wenzhou Medical University (Wenzhou, China); MD, Internal Medicine, Hainan Medical University (Haikou, China)

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Victor Lin, MS

Graduate Student

MS, Medical Science, Drexel University College of Medicine (Philadelphia, PA); BS, Biology, Washington University (St. Louis, MO)

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Gabriella Mraz, BS

Research Technologist

BS, Chemistry & Biology, Ripon College (Ripon, WI)

Alumni

Amber Mull, PhD
Research Associate

Antos Shakhbazau, PhD
Research Associate

Ashwini Zolekar
Research Specialist/Lab Manager

News

Rare Genetic Disorder Research Opens Door to Novel Melanoma Therapy
Genetic Engineering & Biotechnology News | November 6, 2018

Team studying rare disorder discovers novel way to target melanoma
EurekAlert! | November 5, 2018

Generation of hiPSCs
Genetic Engineering & Biotechnology News | November 14, 2014

Recent Publications