Education and Training
BA –UNC at Chapel Hill —1969. Undergraduate studies in biology and chemistry.
PhD —UNC at Chapel Hill—1974. Graduate studies in endocrinology and neuroendocrinology.
University of California in San Diego (UCSD), CA—training with Drs. Gordon Sato and John Holland in cell biology and virology (NIH postdoctoral fellowship)
Jackson Laboratories in Bar Harbor, Maine—training with Dr. Kenneth Paigen in genetics
Pasteur Institute in Paris, France—Training with Drs. Francoise Kelly and Francois Jacob in cell biology
Areas of Interest
We have been studying the core mechanisms that govern differentiation and tissue-specific gene expression of epithelia. They comprise those dictated by the epithelial-mesenchymal cell-cell relationships and those defined by stem cell and maturational lineage biology. The epithelial-mesenchymal cell-cell relationships are driven by synergistic effects of soluble signals (autocrine, paracrine, endocrine) with the effects of the extracellular matrix, an insoluble complex of collagens, adhesion molecules, proteoglycans and factors bound to these matrix components. Tissue-specific gene expression is mediated by matrix-hormone/growth factor synergistic effect. Most of these influence posttranscriptional regulatory mechanisms (translation, mRNA stability, protein stability, etc.). Transcriptional regulation is governed primarily by soluble signals in combination with proteoglycans and more specifically with those soluble signals in combination with defined epitopes of the proteoglycan’s glycosaminoglycan (GAG) chains. The most potent of these GAG chains are forms of heparins with specific sulfation patterns.
The epithelial-mesenchymal cell-cell mechanisms are subsumed by ones involving lineage-dependent phenotypic traits of stem cells and their maturational lineage descendants. The maturation of the epithelia is coordinated with that of their mesenchymal cell partners. This results in lineage-dependent expression of paracrine signals, receptors and extracellular matrix components.
If recognition of these phenomena is utilized in strategies for handling cells, then these cells (of any tissue and from any species) can be maintained as stem cells or as one of the intermediates in the maturational cell lineages or as fully mature cells ex vivo in monolayer cultures, in organoid cultures (floating aggregates of the cells), or as bioartificial organs in perfusion bioreactors. Optimization of the differentiation depends on using serum-free, wholly defined conditions of soluble signals and of extracellular matrix extracts or components.
These principals also form the foundation for strategies for cell therapies for dysfunctional tissues or organs. Transplantation of mature cells can confer some relief of dysfunctions, but with very transient effects. Long-term effects (and even cure) of dysfunctions occurs with transplantation of stem cell organoids comprised of epithelial stem cells and their mesenchymal stem cell partners.
Proof of these principals has been achieved in experimental studies in liver and pancreas in rodent, pig, and human model systems. The experimental studies have led to successful, completed clinical trials of stem cell therapies for liver dysfunctions in humans in India and with approval for use throughout India. Similar clinical trials are now ongoing in Europe. Although these initial clinical trials have made use of transplantation of stem cells via a vascular route, we are now establishing grafting strategies for transplantation of stem cells into and onto internal organs. The grafting strategies have proven successful in transplanting large numbers of cells into liver and pancreas and are now being tested for their efficacy in correcting hepatic or pancreatic dysfunctions.
The findings and the technologies have been described in detail in publications and patents. The patents have been licensed to biotechnology companies, particularly to Vesta Therapeutics (Bethesda, MD) for clinical uses and to PhoenixSongs Biologicals (Branford, CT) for uses for non-clinical commercial products.
Awards and Honors
Cutter Lab Scholarship
Scholarship to study in Germany for a year
Graduated from UNC with high honors
NIH pre-doctoral and postdoctoral fellowship awards
Sinsheimer career development award
NIH Career Development Award
American Cancer Society (ACS) Executive Award
Advisor to NASA on biological studies in space
Carl Vestling Lectureship
UNC Inventor of the Year
Associate editor at Hepatology
External advisory board member of the Institute of Translational Hepatology (Beijing 302 Hospital, Beijing, China)
Adhoc member of multiple NIH and ACS Study Sections
Member, Lineberger Cancer Center
Founder and chief scientific officer of Vesta Therapeutics (Bethesda, MD)
Founder and chief scientific officer of PhoenixSongs Biologicals (Branford, CT)
Advisor to industry (biotechnology companies and pharmaceutical companies)