Martin Lab History
Evolution of the Martin Lab
The Martin Lab has been focused on understanding the unique plasticity of smooth muscle cells that allows them participate in growth and repair of the vasculature, but also contributes to cardiovascular diseases. The phenotypic switching in smooth muscle cells occurs in response to environmental cues which include changes in growth factors, cytokines, prostaglandins, mechanical stress, extracellular matrix, interaction with other cell types, and nutrient availability. These signals are interpreted by cell surface receptors and are transduced to the nucleus to alter gene expression. Dr. Martin’s diverse training and collaborations have allowed her lab to investigate many facets of this process, including prostaglandins and adipokines, cellular signaling cascades, transcription factors, and epigenetic regulation of gene expression in SMC.
Dr. Martin began her training with a PhD in Physiology and Biophysics at Case Western Reserve University. Her thesis work included studying muscle-specific transcription factors at CArG elements with Dr. Kenneth Walsh, and regulation of purinergic receptors in myeloid differentiation with Dr. George Dubyak. She next pursued postdoctoral studies on GPCR at Harvard Medical School with Drs. Craig and Norma Gerard. In a postdoctoral fellowship in Cell Biology at Harvard Medical School, Dr. Martin began her long-standing interest in the PI3K/mTOR pathway, studying S6K2 regulation with Dr. John Blenis.
The Martin Lab at Dartmouth
Dr. Martin began her faculty career at Dartmouth Medical School in Vascular Surgery and Pharmacology in 2000. Working closely with Vascular Surgeons Drs. Richard Powell and Eva Rzucidlo, Dr. Martin began to apply her expertise in cell biology and mTOR signaling to the study of vascular smooth muscle cells (SMC). The team discovered that the mTORC1 inhibitor rapamycin actively promoted SMC differentiation by transcriptional mechanisms. This discovery has been the foundation of the ongoing studies in the Martin Lab, which has since identified multiple novel mediators and mechanisms that regulate SMC phenotype. These include rapamycin, adiponectin, prostacyclin, Akt2, GATA-6, FoxO4, and others.
Prostacyclin and SMC Phenotype
At Dartmouth, the Martin Lab began the long-standing collaboration with Dr. John Hwa (Pharmacology and Toxicology) which led to the surprising discovery that the vasodilator prostacyclin promotes the SMC differentiation, a novel mechanism underlying the cardioprotective effects of prostacyclin. In another collaboration with Dr. Roger Young (Obstetrics and Gynecology), the team applied these findings to explain the long-standing paradox of why the smooth muscle relaxant prostacyclin is highly upregulated in myometrium prior to labor onset. The team found that prostacyclin potently induces transcription of multiple components of the contractile machinery (actin, myosin, connexins, etc) in uterine SMC. Identifying prostacyclin as a key mediator in myometrial activation has implications for both preterm labor and induction of labor at term.
The Martin Lab at Yale
The Martin Lab moved to the Yale Cardiovascular Research Center in September 2009, expanding their studies in SMC phenotypic modulation to multiple in vivo models including intimal hyperplasia, atherosclerosis, transplant vasculopathy, and obesity and diabetes. Early studies included identifying the adipokine adiponectin as a paracrine-acting myocyte-derived differentiation signal. Other studies have been highly focused on understanding the differential roles of Akt isoforms and their downstream targets in SMC intimal hyperplastic response. The recent identification of Tet2 as a novel epigenetic master regulator of SMC phenotype has broadened the scope of the lab from signaling and transcriptional regulation to studying how these processes intersect with epigenetic regulators to influence gene expression in phenotypic switching. Newer studies are additionally integrating the impact of obesity and diabetes on SMC in cardiovascular disease. The overall goal of the lab remains to identify novel mechanisms that govern SMC phenotype in order to develop better preventive and therapeutic strategies for cardiovascular disease.