UTMB

Henry F. Epstein, M.D.,
Professor

Faculty

Henry F. Epstein, M.D.

About the Lab

The current focus of Dr. Epstein's laboratory is on characterizing novel proteins regulating the cytoskeleton. Genetic analysis is now turning to mouse lines as well as Caenorhabditis elegans to facilitate medical applications.

Biochemical and genetic studies on the C. elegans model as well as in various fungal species have demonstrated that a novel molecular chaperone is required for the proper folding, assembly, and function of myosins and myosin-like protein motors. The chaperone protein, named UNC-45 after the canonical gene in C. elegans, binds the well-known molecular chaperone Hsp90 as well as myosin. In mice and humans, two UNC-45-like genes are present and encode closely related but distinct isoforms. One isoform is present in many cell types and appears necessary for cell division and membrane fusion; the other isoform is expressed predominantly in heart and skeletal muscle and is necessry for sarcomere organization. The UNC-45 mammalian homologues may prove to be important targets for genetic and pharmacological intervention in certain cancers and heart failure.

Dr. Epstein's laboratory was part of the international consortium that cloned and identified the myotonic dystrophy locus. The major protein product of that locus, myotonic dystrophy protein kinase (DMPK), is a serine-threonine protein kinase related to Rho kinase and other regulators of cell cycle, cytoskeletal, and membrane-associated processes. DMPK appears to team up with Rho kinase and myosin light chain kinase (MLCK) to regulate the assembly and function of myosin and the actin cytoskeleton. The membrane-associated regulators Rac-1 and Raf-1 activate DMPK whereas the cytosolic RhoA activates Rho kinase. DMPK and negative regulator of cytoskeletal myosin II. Our hypothesis is that DMPK along with MLCK activates the membrane-associated cytoskeleton whereas Rho kinase activates the cytosolic system. The DMPK system may be particularly important in the development and function of highly plastic synapses related to learning and memory of the brain.

Interview with Dr. Epstein

– by Keerthi Gottipati, 2nd year BMB Student

Talking to Dr. Epstein is like listening to tales from fantasy land. He is a mountain of knowledge and anecdotes. Being one of the most senior scientists in UTMB he brings together the old and new schools of thought and bridges the gap between pure and applied biochemistry and molecular biology.

Dr. Epstein, though at first glance gave me the impression of being a staunch old-school scientist, made me feel right at ease and surprised me with his quick recollection of some indigenous facts about my home town in India which are not known even to people who have lived there for years. Being one among the oldest scientists at UTMB, he carries with him a unique and varied background of medical physiology and physical chemistry.

I miss the environment at Cambridge of everyone dining together, we would openly discuss science and everything was up for debate
– Dr. Epstein encouraging an open dialogue on science with students.

Dr. Epstein brings to UTMB a legacy of scientific excellence. For most of us names like Francis Crick or Arthur Kornberg and Anfinsen (whom he calls the 'Oldest Folder') are legends we read about in science text-books. But for Dr. Epstein these great scientists are the ones who molded his scientific ideologies and career. He talks of his glory days when he worked with legends like Dr.Anfinsen, Dr. Crick (yes the DNA guy) and Dr.Arthur Kornberg (remember DNA replication?). “To most of you,” he adds, “they are just names in textbooks.”

He considers them his scientific idols for their dedication to the highest ideals in science. In addition, Dr. Anfinsen, he adds, constantly encouraged young scientists. He leans forward on his table to show me a picture of the nobel-prize father-son duo Arthur Kornberg, who won the 1959 Nobel Prize in Medicine and Roger D. Kornberg, Arthur's son, who won the 2006 Nobel Prize in Chemistry. He said Dr. Kornberg organized his department by recruiting scientists who he thought were 'smarter than him', which he believes was and still is an unbeatable strategy to improve the quality of the department.

When I asked him what drove him to stay on in research, he smiled and said 'the highs of discovery'. He loves to contemplate about science and believes that every piece of discovery fits into a larger fabric. He said he feels lucky that he could contribute to that fabric with his work.

When asked to describe the environment in his lab and his interaction with his students, he said he meets with every person in his lab in person and expects everyone to be involved in the group meetings. Not just that, he makes these meetings even more energetic by teaming up with three other labs (those of Dr. Oberhauser, Dr. Barral and Dr. Sutton). With feedback from different areas, he keeps the science in his lab integrated and wholesome. His motive is for everyone to know about everything that goes on in the lab and actively participate in critical discussions.

I particularly encourage my students to write the first draft of their papers completely all by themselves. I believe the student in my lab should get all the possible training in scientific method before he/she graduates.
– Dr. Epstein, on what he expects from his students.

Dr.Epstein is one of the few faculty at UTMB who actually dines at the student center. The reason, he says, is that he likes interacting with students and is there to invite students to talk to him, to discuss their work, to talk about anything they would like to talk about. He stresses that interaction with peers and other scientists is a major contributing factor to the quality of science. He professes an honest disclosure of facts and an open-minded discussion of the pros and cons of the project. He encourages students to join him for lunch and talk about their work, who knows we might just have a nobel-prize winning idea just by talking things out.

When I asked him what made him come to UTMB apart from being recruited, he said Baylor being his alma mater for 25 years, he had had the opportunity to work with faculty here at UTMB and found the work promising. Under the aegis of the Molecular Biology Educational Track and the Sealy Center for Structure biology he envisions integrating and expanding his present genetic and molecular biology research into structural, physical and biophysical venues.