Biography

Dr. Kellems received his PhD from Princeton University for highly cited research that illustrates how cells target the co-translational import of nuclear-encoded proteins into mitochondria.   The fundamental importance of this work is evident from the fact that it continues to be cited on a regular basis more than 50 years after publication.  Postdoctoral research at Stanford University employed emerging techniques in molecular genetics to discover gene amplification as a novel mechanism of drug resistance in mammalian cells. These groundbreaking discoveries have had a major impact in cancer biology and laid the foundation for the discovery of amplified proto-oncogenes in cancer cells, which often reside on extra-chromosomal DNA (termed EC-DNA),currently an area of active cancer research.  Gene amplification also plays a major role in biotechnology where co-amplification is the most frequently used method to overproduce proteins of medical importance in mammalian cells.

Following his postdoctoral fellowship, Dr. Kellems accepted a faculty position at Baylor College of Medicine, where he continued his interest in gene amplification and developed patented gene amplification technology based on adenosine deaminase (ADA).  The technology was licensed by Baxter Healthcare and used to produce Factor VIII and Factor IX to treat hemophilia.

While at Baylor, Kellems initiated a new research program to understand the metabolic and molecular basis of immunodeficiency associated with ADA deficiency in humans, at that time a newly discovered human genetic disorder.  For this purpose, his lab devised a novel two-stage genetic engineering strategy to construct ADA-deficient mice that served as an excellent mouse model for ADA-deficiency in humans.  Research from the Kellems’ lab showed that the immunodeficiency resulted from impaired T-cell development in the thymus, resulting from the ADA-deficiency.  These mice were successfully used in pre-clinical tests to show that gene therapy could be  used to treat ADA-deficiency and restore immune function.  The clinical trials with ADA-deficient children that followed were among the first, and remain the most successful example of gene therapy to treat a human genetic disorder. While at Baylor Kellems served as Director of the Graduate Program in Biochemistry and Molecular, Co-Director of an NIH funded Medical Scientist (MD/PhD) Training Program and as Director of an NIH funded Program Project entitled “Gene Therapy for Genetic Disease.”

In 1997 Kellems was recruited to the University of Texas McGovern Medical School to Chair the Department of Biochemistry and Molecular Biology, a position he held for 28 years.   While at McGovern, Kellems continued his research on ADA-deficiency and showed that, in addition to the immunodeficiency, the mice also have numerous other phenotypes resulting from chronically high levels of adenosine that activate adenosine receptors present on many cell types. He and others have used these mice as a discovery platform to determine that excessive adenosine signaling contributes to other pathological conditions, including erectile dysfunction, pain, hearing loss, cognitive decline, lung fibrosis, renal disease and impaired wound healing.

While at McGovern, Kellems expanded his interest in immunology to include autoimmunity, and its role in preeclampsia, a serious hypertensive condition of pregnancy. He and his colleagues showed that women with preeclampsia harbor autoantibodies that activate the AT1 angiotensin receptor and were the first to show that these autoantibodies (termed AT1-activating autoantibodies or AT1-AA) cause the defining clinical features of preeclampsia when injected into pregnant mice. This highly cited research suggests that preeclampsia is a pregnancy-induced autoimmune condition characterized by the presence of pathogenic autoantibodies that contribute to hypertension and renal impairment by activating AT1 receptors.  Recent studies have highlighted the role of tissue transglutaminase in the posttranslational modification of AT1 receptors as a contributing factor to autoimmunity and hypertension.

As department chair, Dr. Kellems provided academic and administrative support for a multidisciplinary group of faculty members leading independent research programs ranging from atomic level structural biology investigations to preclinical and translational studies using mouse models of human disease.  Under Kellems’ leadership the department routinely ranked among the top 20% of US medical school biochemistry  departments based on NIH funding.

Dr. Kellems received nearly 35 years of research support from the National Institutes of Health and co-authored more than 165 papers that have been cited over 15,000 times (H index 75). Throughout his career Dr. Kellems mentored a large number of graduate students, postdoctoral fellows and junior faculty members.  He has received numerous honors and awards including the President’s Scholarship from Bellarmine University, a NIH Predoctoral Traineeship at Princeton University, a NIH Postdoctoral Fellowship at Stanford University, a United States Public Health Service Research Career Development Award at Baylor College of Medicine, the President’s Recognition of Excellence Award at UTHealth Houston and the Bob and Hazel Casey Endowed Chair in Biochemistry from McGovern Medical School.  He is also an inventor on five U.S. patents, including one that was licensed by Baxter Healthcare to produce Factor VIII and Factor IX to treat hemophilia.  Dr. Kellems has consulted extensively with major biotechnology and pharmaceutical companies and served as an expert witness in patent litigation.