Six scientists selected as endowed scholars
By Deborah Wormser
UT Southwestern Medical Center leaders recently announced the selection of six outstanding scientists as the newest Endowed Scholars in Medical Science. With the addition of the 2016-2020 class, a total of 94 selected investigators have launched their research careers through the prestigious program, now in its 20th year.
Established in 1998 with $60 million in philanthropic funds, the program provides seed money and four-year support for early-career investigators to carry out independent, cutting-edge research projects. Each Scholar undertakes basic science or is a clinical researcher who joins the faculty as a tenure-track Assistant Professor.
“This was an especially successful year for the Endowed Scholars Program,” said Dr. Eric Olson, Chairman of Molecular Biology and Director of the Hamon Center for Regenerative Science and Medicine. “This program is the lifeblood of UT Southwestern, infusing the institution each year with the top early career investigators in the country. We have very high expectations for this class and look forward to enabling them to achieve their highest potential.”
Endowed Scholars Class 19: 2016-2020
Virginia Murchison Linthicum Scholar in Medical Research
Dr. Xiaochen Bai, Assistant Professor of Biophysics and of Cell Biology, thinks of himself as a molecular biologist and electron microscopist who specializes in image processing on cryo-electron microscopes (cryo-EM) like those at UT Southwestern’s advanced cryo-EM facility, which uses automation and sensitive detectors to view flash-frozen samples.
One line of his research has implications for neuroscience, specifically the accumulation of amyloid–β (Aβ) and amyloid precursor protein (APP) in the brain, critical components of the amyloid plaques associated with the development of Alzheimer’s disease. APP reacts with an enzyme called γ-secretase in order to produce Aβ. It is hypothesized that mutations in γ-secretase lead to the production of the Alzheimer’s-triggering form of Aβ. Under that hypothesis, finding a drug that selectively targets the specific enzyme sites at which γ-secretase and APP bind would be crucial to developing a treatment for Alzheimer’s disease.
Other planned research will take a deep dive into cell surface receptors, which allow communication between the outside and inside of a cell. In research that could lead to new cancer therapies, he will study receptor tyrosine kinases (RTKs), which play important roles in many normal body functions.
Dr. Bai, who trained at Tsinghua University in Beijing, China, comes to UT Southwestern from the Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, U.K., where he was a senior investigator scientist and before that a Marie Curie Fellow.
W.W. Caruth, Jr. Scholar in Biomedical Research
Dr. Don Gammon, Assistant Professor of Microbiology, has created novel modeling systems in which to study virus-host interactions in invertebrates. His work is expected to lead to a better understanding of the innate immune mechanisms that eukaryotic organisms use to restrict viral replication as well as the strategies that viruses use to counter those restrictions.
Dr. Gammon was one of only five Canadian graduate students chosen to attend the annual Lindau Nobel Laureate meeting in Germany. There, he met Dr. Craig Mello of the University of Massachusetts Medical School and subsequently joined the Mello lab as a postdoctoral researcher.
In the Mello lab, Dr. Gammon created novel virology modeling systems based on some unique observations. First, he serendipitously discovered that two RNA-encoding arboviruses – members of an emerging group of viral pathogens transmitted from blood-feeding insects to humans – cause only abortive infections in butterflies and moths (Lepidopterans). He also found that those arboviruses can replicate in Lepidopteran cells when host immunity becomes compromised via co-infection with other viruses, including poxviruses.
He used those findings to create a novel modeling system that revealed the first insights into RNA virus immunity in Lepidopteran insects and identified a new family of poxvirus proteins that promote virus replication in both Lepidopteran and vertebrate hosts.
Recently, Dr. Gammon also established a new arbovirus modeling system in C. elegans. Research using his new invertebrate modeling systems could potentially lead to bioinsecticides for gypsy moths or insights into the pathogenesis of arboviruses, a group that includes Zika virus, West Nile virus, and dengue virus.
Effie Marie Cain Scholar in Medical Research
Dr. Lukasz Joachimiak, Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Biochemistry, has a passion for exploring how structural biology and biochemistry relate to human disease. His laboratory specifically studies how protein-based molecular recognition drives mechanisms underlying neurodegenerative diseases. His cross-discipline approaches are expected to capitalize on recent advances in mass spectrometry and protein engineering to help answer important questions in some of the world’s most devastating conditions, including Alzheimer’s and prion diseases.
Dr. Joachimiak was recruited from Pacific Biosciences in California, where he used computational structural biology to engineer proteins. He previously was a postdoctoral researcher at Stanford University, where he studied the structural and mechanistic properties of the eukaryotic chaperonin TRiC/CCT. That complex is comprised of two rings of eight paralogous subunits that participate in the folding of many essential proteins.
In the course of that work, Dr. Joachimiak was first author on three papers – published in Cell Reports (2012), Structure (2012), and Cell (2014) – that among other things suggested an entirely different mode of conformational changes and molecular mechanics for the TRiC/CCT complex than had been previously envisioned. Those findings may prove important to many diseases characterized by misfolding, including Huntington’s disease and other neurological conditions.
Dr. Joachimiak, a University of Wisconsin graduate (biochemistry), earned his Ph.D. at the University of Washington. While in Seattle, he used computational methods to engineer protein complexes. He also was first author of papers in Nature Structural & Molecular Biology (2004) and a Molecular Cell (2011). His graduate work focused on how computational methods alone can predict new functions in protein complexes.
Southwestern Medical Foundation Scholar in Biomedical Research
Dr. Takashi Kitamura, scheduled to arrive May 1 as an Assistant Professor of Psychiatry with a secondary appointment in Neuroscience, was lead author of a 2009 Cell study showing that adult neurogenesis modulates fear memory. Subsequent studies done as a postdoctoral researcher in the laboratory of Dr. Susumu Tonegawa at the RIKEN-MIT Center for Neural Circuit Genetics and published in Science, the Proceedings of the National Academy of Sciences, and Neuron established new circuit and cellular mechanisms of memory mediated by the hippocampus and entorhinal cortex, which are both involved in episodic memory formation.
“Episodic memory consists of associations of objects, space, and time. My previous studies identified specific neuronal populations – the ocean cells and the island cells – that encode these unique physiological properties, that is the ‘where’ and ‘when’ of episodic memory,” Dr. Kitamura said. “The goal of my laboratory here at UT Southwestern is to understand neural circuit mechanisms and the computations that allow animals to associate events that are separated by time into a complete episodic memory.”
Dr. Kitamura completed his undergraduate and graduate work in biology at Kyushu University, Fukuoka, Japan, where he worked as a research assistant and became a research fellow. He followed that with a postdoctoral research fellowship at the Mitsubishi Kagaku Institute of Life Sciences in Japan. In 2009, he became an Assistant Professor of Biochemistry at the University of Toyama in Japan prior to his position at the RIKEN-MIT Center in Boston. On April 19, he will receive The Young Scientists’ Prize for Science and Technology from the Japanese government at a ceremony in Tokyo.
Thomas O. Hicks Scholar in Medical Research
Dr. Ram Madabhushi, Assistant Professor of Psychiatry, of Cell Biology, and of Neuroscience, specializes in research on genomic integrity and epigenetic regulation of gene expression in the brain under both natural and pathological conditions. It is widely believed that depression, schizophrenia, and addiction are all influenced by epigenetic mechanisms. After graduating from the University of Bridgeport in Connecticut, Dr. Madabhushi studied molecular biology for his doctorate at the Weill Graduate School of Cornell University in New York. He joins the UT Southwestern faculty following postdoctoral research at the Massachusetts Institute of Technology.
“The highlight of my postdoctoral research is the surprising discovery that physiological neuronal activities, including learning behaviors, cause neurons to incur DNA breaks,” he said. “Because DNA breaks are regarded as cytotoxic lesions, this phenomenon raises intriguing questions about how the formation and repair of DNA breaks in response to physiological neuronal activity is controlled, and whether the dysregulation of these processes could contribute to diseases, including neuropsychiatric disorders.
“Addressing these questions will be the focus of my immediate efforts as an independent investigator at UT Southwestern.”
Dr. Madabhushi said it is now clear that activity-induced DNA breaks are linked to gene expression in a number of cell types and systems, including genes activated by estrogen, androgens, and insulin signaling. The aberrant repair of these DNA breaks, he said, has been linked to the development of certain cancers, which will provide an additional interest of his laboratory.
Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Bill S. Vowell
Dr. Fei Wang is an Assistant Professor of Internal Medicine in the Center for Autophagy Research with a secondary appointment in Cell Biology. His broad research goals are to assemble all the pieces of the cellular puzzle to reveal its structure and function, and he is approaching his work from several directions.
“Proteins and lipids are two major components of most functional units or structures within a cell. The interactions between lipid membranes and proteins are among the most challenging topics in biological studies,” he said. After years of working on protein targeting – the transporting of the appropriate proteins within and outside a cell – and insertion of the proteins into a membrane, he was attracted to the parallel but mechanistically distinct cellular process of vesicle targeting and fusion to a growing or steady membrane.
His investigations of autophagy, the cellular housekeeping and recycling mechanism, currently are focused in yeast and mammalian cellular development. That research could lead to treatments for autophagy-related diseases, including some forms of cancer and neurodegenerative diseases. To aid his research, Dr. Wang developed a distinct chemical genetics tool for studying how autophagy machinery is repurposed for sporulation (the creation of spores in yeast).
Dr. Wang completed his undergraduate and master’s degrees at China’s highly regarded Fudan University. He then attended the University of Massachusetts Amherst, where his Ph.D. thesis was the basis for a first-author study published in The Journal of Cell Biology. Dr. Wang went on to conduct postdoctoral research at Harvard University, which led to his serving as first author on a study in Nature in 2014.
Dr. Olson holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research.
