Four outstanding scientists receive this year’s DeBakey awards
By Ruth SoRelle, M.P.H.
Four scientists from different disciplines were chosen this year to receive the 2008 Michael E. DeBakey, M.D., Excellence in Research Awards.
"Each award winner has set new standards in the understanding of cellular activities and opened doors for new treatments of disease," said William T. Butler, M.D., interim president at Baylor College of Medicine. The four received their awards in ceremonies Jan. 14, at which they also described their work.
The awards honor faculty members who have made the most significant published scientific contribution to clinical or basic biomedical research during the past three years. Each receives a Michael E. DeBakey, M.D., Excellence in Research medallion and an unrestricted fund in support of their research program, along with a celebration dinner for the awardee's laboratory.
The awardees include:
Thomas Zwaka, M.D., Ph.D.
Assistant Professor
Center for Cell and Gene Therapy
Stem Cells and Regenerative Medicine Center
Department of Molecular and Cellular Biology
Thomas Zwaka, M.D., Ph.D., had already trod the less traveled scientific path in the field of embryonic stem cells when he came to BCM more than four years ago, but his latest work opens new doors in understanding how embryonic stem cells continue to renew themselves as undifferentiated cells and in pointing the way toward understanding the signals that cause them to start down the road to becoming a specific type of cell or tissue.
While still at the University of Wisconsin, Zwaka was the first to establish homologous recombination (the exchange of genetic material between similar strands of DNA) as a way for modifying human embryonic stem cells. As his mentors Peggy Goodell, Ph.D., director of the STaR Center, and Malcolm Brenner, M.D., Ph.D., director of the Center for Cell and Gene Therapy, stated in recommending him for the award, "The ability to manipulate and modify these stem cells is the cornerstone of developing new therapies, just as the manipulation of mouse stem cells has been instrumental in our understanding of mammalian biology over the past 20 years." They called his paper "landmark" and noted that he has followed that up with a focus on the novel theory that enzymes called caspases are involved in the early events involving tissue differentiation in embryonic stems and embryos.
Caspases are known to be involved in apoptosis or programmed cell death. However, Zwaka noted that levels of specific caspases peaked when embryonic stem cells were differentiating. The cells that expressed high levels of these caspases differentiated and did not die. In following that line of thought, he identified that one of the classic proteins that play a role in embryonic stem cell self renewal – NANOG – may itself be a target of a caspase. When NANOG is cleaved or cut, it can no longer cause the cell to self-renew. Instead, it begins to differentiate.
Along the same line, he identified another protein he called Ronin that is also cleaved or cut during the process of embryonic stem cell differentiation. Ronin, he showed, regulates the ability to embryonic stem cells to become any type of cell (pluripotency) and that it works independently of other factors such as NANOG and Oct4 that have already been identified as part of the pluripotency equation.
"The discovery of an independent pathway for pluripotency raises the possibility that Ronin, alone or in combination with other factors, may be able to be used to induce pluripotentiality in non-stem cells."
Jianpeng Ma, Ph.D.
Professor
Biochemistry and Molecular Biology, BCM
Professor, Bioengineering, Rice University
Jianpeng Ma, Ph.D., focuses on the relationship between structure and function in the study of biological macromolecules and supramolecular complexes, which marry the fields of chemistry, biophysics and structural biology. When a substrate or particular substance binds to an enzyme or a drug to its target, and when signals go between cells, the processes that involve all partners in the reaction are highly interactive in a selective sense. His studies look at these processes. In recent years, he has focusd on the study of biological molecules using X-ray crystallography, which involves the study of the diffraction of X-rays through a molecule to determine location of each atom within it. Ma has devised a particular mathematic method of studying large biological molecules to provide accurate structural models and, more important, a description of the dynamics involved in the activities of these molecules and their interactions with others.
His normal-mode-based method for modeling works well with high and low-range of resolutions of models, which means it can be used in a broad spectrum of biomolecular structures. Among his most notable finding is the use of the normal-mode-based refinement of the potassium channel KVL.2 that enabled visualization of nearly one-third of the mass of the channel, a portion that had not been previously seen in models.
His Harvard University mentor, Nobel Laureate William N. Lipscomb, said of him, "The success of Dr. Ma’s normal-mode method in improving structural refinement is unparalleled by any other method in the field of structural biology over the past twenty years. This new approach is revolutionizing not only the process of structural refinement, but also the accurate interpretation of the protein structure-function relationship. Furthermore, the method’s impact on molecular biology will only grow, as diffraction data for large flexible complexes at limited resolutions are becoming ever more abundant."
Scott Pletcher, Ph.D.
Associate Professor
Huffington Center on Aging
Department of Molecular and Human Genetics
How long do people live and why? Dr. Pletcher seeks to answer those questions using model organisms, such as fruit flies. In 2007, a paper published in Science described his research showing that just the odor of food shortened the lives of fruit flies, research that Gretchen Darlington, Ph.D., interim director of the Huffington Center and Arthur Beaudet, M.D., chair of molecular and human genetics, called a "paradigm shift" in the field in a letter nominating him for the award. In fact, they noted that the "mere perception of nutrient availability may reverse a subset of the physical alterations induced by dietary restriction and limit its benefits." In a 2008 report in the journal Cell, he and his colleagues challenge the notion that the caloric content is the most important aspect of diet. Their findings indicate that subtleties revolving around diet composition play an important role in lifespan and healthy aging.
N. Tony Eissa, M.D.
Professor
Department of Medicine - Section of Pulmonary, Critical Care, and Sleep Medicine
Eissa described the physiologic aggresome, in which cells regulate inducible nitric oxide synthase – an important host defense protection – using these "holding stations" for aggregated and misfolded proteins. The 2005 study by him and his colleagues indicate that formation of the aggresome in response to misfolded proteins may simply represent acceleration of an already accepted physiologic regulatory process.
Understanding the regulation of inducible nitric oxide synthase may provide basis for the design of a host of therapies. Eissa’s description of CHIP (carboxy terminus of Hsp70-interacting protein) and its role in the formation of the aggresome could prove valuable in identifying treatment strategies.
Eissa has also forged new ground in the study of autophagy, a process identified in almost all eukaryotic cells, identifying Toll-like receptor 4 as a previously unrecognized environmental sensor for this process. Autophagy is the method by which cells self-digest their own components, often as a result of stress or degeneration. His work opened new doors for potential therapeutic strategies to outsmart pathogens by using Toll-like receptor to modulate autophagy. He has also used autophagy to enhance vaccine efficiency against Mycobacterium tuberculosis in mice.
