Eight members of MD Anderson faculty named AAAS fellows
Their responsibilities may range from exploring the intricacies of biostatistics to bringing new drugs more rapidly to the patient, but eight faculty members from MD Anderson Cancer Center all share one honor — being named as fellows by the American Association for the Advancement of Science.
“It is indeed a tremendous accomplishment to be selected as an AAAS Fellow,” said Ethan Dmitrovsky, M.D., provost and executive vice president at MD Anderson. “MD Anderson is known worldwide for its leading patient care, research and education, and this recognition is a wonderful tribute to the men and women who, each day, bring their knowledge and dedication to our mission.”
AAAS Fellows are elected by existing members of the 140-year-old organization, the world’s largest general scientific society. MD Anderson now has 32 AAAS Fellows on its faculty, with 23 elected in the last four years.
The AAAS Fellows named includes:
Ronald DePinho, M.D., professor of Cancer Biology and president of MD Anderson
DePinho’s investigations have produced an array of discoveries leading to better methods of early cancer detection, improved cancer patient care and new cancer drug development. The range of his research includes cancer drug and biomarker development, cancer gene discovery, stem cell biology and development of genetically engineered mouse models to study cancer in humans. He was the first to show that the Myc family of oncogenes (cancer-causing genes) function through common cell signaling pathways to turn healthy cells malignant. DePinho established the concept of “tumor maintenance” to address the question of whether an original cancer-causing oncogene can remain active in maintaining a tumor despite the accumulation of many alterations in DNA during the malignant transformation process. This concept has contributed to cancer-drug development by guiding identification of new therapeutic points of attack, as well as novel biomarkers that measure a patient’s response to a drug during a course of treatment. His research also provided some of the first evidence that the p53 gene can suppress the development of some cancers by stimulating cell death. DePinho and Robert Eisenman, Ph.D., discovered a co-repressor complex that links a transcription factor and chromatin regulation in suppressing cancers. His lab also provided the first genetic evidence that a familial melanoma gene serves as a potent tumor suppressor in melanoma and other cancers. His most notable contributions concern the link between advancing age and increasing risk of cancer. He established three factors that unite to cause DNA rearrangements that spur many cancers. Beyond cancer, DePinho has established the role of telomere dysfunction in acquired and inherited degenerative disorders such as end-stage liver failure. His findings suggest there may be a “point of return” in which medicines might help severely aged organs to recover a youthful state. At MD Anderson, DePinho has established the Institute for Applied Cancer Science, where his lab focuses on basic-to-translational research programs for brain, colorectal, pancreatic and prostate cancers, as well as aging and neuro-degeneration.
Dickey’s investigations include the study of lung epithelial cells, which show great plasticity in structure, function and gene expression. In response to allergic inflammation, airway secretory cells produce large quantities of polymeric mucins, and his laboratory studies the molecular mechanism of mucin secretion, focusing on Munc18, Munc13, Syntaxin and Synaptotagmin proteins. Epithelial signaling by the beta-2-adrenoceptor promotes allergic inflammation and mucin production. Dickey’s lab is studying the molecular mechanism of this phenomenon in collaboration with Richard A. Bond of the University of Houston. In response to Toll-like receptor signaling, airway epithelial cells develop a high level of resistance to microbial infection, and Dickey is investigating the molecular mechanism in collaboration with Scott E. Evans, M.D., associate professor of Pulmonary Medicine, and developing a clinical therapeutic to prevent pneumonia. Airway inflammation also contributes to epithelial carcinogenesis, and Dickey has established mouse models of this phenomenon and is dissecting mechanisms in collaboration with Seyed J. Moghaddam, M.D., assistant professor of Pulmonary Medicine. For each of these programs, the laboratory uses primarily a mouse genetic approach, generating knockout and transgenic mice and analyzing their responses in conditions of pathophysiologic change.
Gandhi's research focus is in the development of therapeutics for hematological malignancies. She uses biologic, biochemical and molecular approaches to understand the metabolism and mechanism of action of different groups of chemotherapeutic agents. Based on mechanism of action of novel agents and biology and pathophysiology of the disease, her group tests these drugs in hematological malignancies. Currently, her group is working on several targets such as Met receptor tyrosine kinase in myeloma, Bcl-2 antagonists in leukemias, inhibitors of Pim kinase, Bruton’s tyrosine kinase as well as PI3 kinase in heme malignancies, and novel small molecule inducers of apoptosis. Her research is translational in nature and her group validates the laboratory-tested hypotheses in the clinic using target tumor tissues. Based on mechanisms of action of chemotherapeutic agents, they also test and develop novel combination strategies. Gandhi has published more than 250 articles and serves on the editorial board of several journals, including Clinical Cancer Research and Leukemia and Lymphoma.
John Mendelsohn, M.D., professor of Experimental Therapeutics, former president of MD Anderson
Mendelsohn served as president of MD Anderson from 1996 to 2011 through an incredibly productive period of nearly 15 years, during which time the institution more than doubled in size. He has an international reputation for his research on how the binding of growth factors to receptors on the surface of cells regulates cell functions. Mendelsohn and collaborators produced the monoclonal antibody 225, which inhibits human cancer cell proliferation by blocking the signaling pathways that are activated by the receptors for epidermal growth factor. His subsequent research in the laboratory and the clinic pioneered the universally adopted concept of anti-receptor therapy, which targets key cell signaling pathways as a new form of cancer treatment. Antibody 225 (commercially known as cetuximab or Erbitux) against the receptor for epidermal growth factor was approved by the U.S. Food and Drug Administration for treatment of colon cancer in 2004 and for head and neck cancer in 2006. Mendelsohn is a recognized leader in the areas of clinical and translational research and has developed and tested new cancer therapies that target the genetic and molecular abnormalities that cause the disease. Such targeted drugs open the door to customizing treatment based on the factors that drive an individual patient’s cancer. Mendelsohn’s groundbreaking research in characterizing growth factor receptors and blocking their stimulation of cell proliferation launched anti-receptor therapy as a cancer treatment.
Molldrem’s lab is exploring the development of immunotherapies for leukemia and other hematological diseases through an understanding of T cell immunity against hematopoietic progenitors. Molldrem believes that T cells target and eliminate these progenitors by recognizing determinants of self-antigens when tolerance has been reversed by aberrant self-antigen expression. As models, his lab has studied myeloid leukemia and MDS and has found that CD8 lymphocytes recognized the HLA-A2-restricted PR1 peptide, derived from both P3 and NE, due to aberrant subcellular localization and over-expression.
Piwnica-Worms studies the molecular imaging of signal transduction pathways and protein-protein interactions in vivo. His lab also is studying the dynamic analysis of the NF-kB, beta-catenin and EGFR signaling pathways, genetically encoded reporters for bioluminescence, PET and SPECT imaging, and high throughput screening with siRNA to functionalize the genome. His work also includes investigation of cell-penetrating activatable near-infrared fluorescent peptides for imaging and therapeutic cell-penetrating peptides, mechanisms and regulation of the ATP-binding cassette (ABC) superfamily of transporter proteins, and multi-drug resistance in cancer; radiopharmaceutical chemistry, as well as medicinal utility of metal complexes.
Shete is a genetic epidemiologist with interests in developing statistical methods for genetic data. He is section chief of behavioral and social statistics in the division of quantitative sciences. He currently serves as the principal investigator for a genome-wide association study of head and neck cancer and is principal investigator with Reyes-Gibby, Dr.P.H., associate professor of emergency medicine, for a study of molecular epidemiology of neuropathic pain in head and neck cancer. He is also the principal investigator for studies on innovative multidisciplinary education: the statistical genetics of addiction. His ability to design and undertake creative genetic epidemiological studies in collaboration with other scientists is evidenced by the range of genetic investigations of complex disorders in which he has been involved. Shete is currently director of the biostatistics, bioinformatics and systems biology program at the Graduate School of Biomedical Sciences. Shete has institutional leadership responsibilities as vice-chair of one of the Institutional Review Boards. He was a member of Ethical, Legal and Social Issues Committee and currently is a member of the scientific program committee of the International Genetic Epidemiology Society. He was a charter member of the Cardiovascular and Sleep Epidemiology Study Section for The National Institute of Health. He is a fellow of the American Statistical Association. Currently, he is the editor-in-chief of the Genetic Epidemiology Journal.
Ullrich’s research focuses on the mechanisms underlying UV-induced immune suppression and immune suppression and immunotherapy of pancreatic cancer. He is particularly interested in the role of cell migration in UV-induced immune suppression. None of the energy contained within the UVB wavelengths of sunlight penetrate beyond the skin, so it is unclear how UV exposure induces systemic immune suppression. For years immunologists have recognized that UV-irradiation induces Langerhans cells to leave the skin and migrate to the draining lymph nodes, where they activate immune suppression. His laboratory has been instrumental in elucidating some of the key mechanisms mediating this action, including the activation of natural killer T cells to secrete IL-4 and a possible role for platelet activating factor (PAF). Ullrich has also demonstrated that UV exposure induces dermal mast cells to leave the skin and migrate to the draining lymph nodes, where they mediate immune suppression.