Stem Cell Research

Stem cell research is currently Lin’s major focus.  The type of stem cells of interest is adipose-derived stem cells (ADSC), and the study is both basic science and clinical.  On the basic side, Lin studies molecular mechanisms that mediate ADSC differentiation into neurons, Schwann cells, smooth muscle cells, and endothelial cells.  He also studies molecular markers that can be used to identify and/or to facilitate the isolation of ADSC.  These markers, both positive and negative, include CD31, CD34, and Stro-1.  Of particular interest is Stro-1 because this cell surface protein is widely considered as the most reliable marker for mesenchymal stem cells (MSC, which include ADSC); yet, Lin has found that most of the published data concerning Stro-1 are erroneous.  Importantly, Lin’s research has uncovered that ADSC are vascular stem cells (VSC), which are probably what most types of MSC actually are. On the clinical side, the primary disease targets are erectile dysfunction (ED), urinary incontinence (UI), and diabetes.  For ED, Lin’s research has shown that ADSC was able to restore erectile function in animal models of both neurogenic and vasculogenic ED.  For UI, his research has shown that ADSC was able to greatly improve continence in animal modes of both stress and urge types of UI.  For diabetes, his research has led to the establishment of ADSC cell lines that synthesize and secrete large quantities of insulin and are capable of reducing blood glucose levels in type I diabetic rats.  Several ongoing clinical trials are based on Lin’s animal studies.

Molecular Mechanism of Impotence

Tom Lue, MD Professor of Urology at UCSF, has developed an animal model for studying impotence. Lin is using this model to identify genes that are involved in the development of impotence. His preliminary data showed that a novel variant of the neurological form of nitric oxide synthase (nNOS) might be differentially expressed in normal and impotent animals. Other genes, such as androgen receptor and phosphodiesterases, are also being investigated currently.

Molecular Mechanism of Female Stress Urinary Incontinence

Urinary incontinence is a large social and economic problem. In particular, female incontinence is estimated to afflict approximately 20 million American women. By using an animal model developed by Lue, Lin is currently investigating genes that may be involved in the atrophy of muscles and nerves. He is also comparing genes of several growth factors, neurological receptors, and steroid hormone receptors in normal and diseased urinary bladders and urethras.