Office of Research & Development
See also: Notable Biomedical Research Investigators
The William S. Middleton Award (Middleton Award) is the highest honor awarded annually by the Biomedical Laboratory Research and Development Service (BLR&D) to senior VA biomedical research scientists in recognition of their outstanding scientific contributions and achievements in the areas of biomedical and bio-behavioral research relevant to the healthcare of Veterans. Middleton Award recipients have achieved international acclaim for research accomplishments in areas of prime importance to VA's research mission. The Middleton Award was established in 1960, to honor William S. Middleton, M.D., distinguished educator, physician-scientist, and Department of Veterans Affairs (VA) Chief Medical Director from 1955 to 1963.
For more details see: Program Guide 1202.05: William S. Middleton Award
Point of Contact: Dr. Carol Fowler (Carol.Fowler@va.gov)
Stephen R. Plymate, M.D., from the VA Puget Sound Health Care System was awarded the 2020 Middleton Award in recognition of his basic and translational studies on androgens and their role in metabolic syndrome and prostate cancer as well as the role of insulin-like growth factor (IGF) signaling in prostate cancer progression.
Dr. Plymate’s early work focused on how transport proteins regulate testosterone action in men and women. This work was translational because the measurement of sex-hormone binding globulins (SHBG) in patient blood samples could be used in the diagnosis and treatment responses of metabolic syndrome. His studies of the relationship between androgen and metabolic status in men led to significant revisions in the concept of androgen deficiency and changes in how androgens are administered. He went on to explore the role of IGF signaling in prostate cancer. This work led to clinical trials in advanced and localized prostate cancer which showed that clinical inhibition of the IGF receptor was feasible and safe. While the initial studies did not meet their primary endpoints, his group is continuing to pursue more effective means of inhibiting the IGF pathway for clinical benefit. Dr. Plymate is credited with elucidating those processes that contribute to development of lethal castration resistant prostate cancer and the discovery of androgen receptor (AR) splice variants that lack a ligand binding domain and are therefore predicted to be resistant to all clinically available endocrine therapies for prostate cancer. His research on AR variants has led to better prediction of response to therapy and prognosis of advanced prostate cancer. In addition, his work has led to the development of new drugs that can target AR in novel ways. Dr. Plymate has served as a VA clinician scientist for more than 28 years. Prior to joining the VA, Dr. Plymate served on active duty in the US Army as a physician for 24 years and is considered one of the preeminent leaders in mechanisms underlying the development and targeting of castration resistant prostate cancer. His career exemplifies how basic research performed in his laboratory has informed his clinical trial work which is expected to have a real-world impact on the treatment of lethal castrate resistant prostate cancer, which disproportionately affects the male Veteran population.
The 2019 Middleton Award was awarded to two candidates: Steven M. Dubinett, M.D. from the VA Greater Los Angeles Healthcare System and Michael R. Zile, M.D. from the Ralph H. Johnson VA Medical Center.
Steven M. Dubinett, M.D., from the VA Greater Los Angeles Healthcare System was awarded the 2019 Middleton Award in recognition of his basic to translational studies which have helped to inform his ongoing immunotherapy clinical trials for lung cancer. Dr. Dubinett is nationally recognized for his research that seeks to understand the immunobiology of lung cancer, and for translating that work into clinical trials that seek to bring new treatments to patients. His early investigations found that cells from patients who had non-small cell lung cancer produced mediators that interfered with cellular immune functions at the tumor site. To overcome this immune system malfunction, Dr. Dubinett developed human dendritic cell vaccines using gene modification techniques to help instill an augmented immune response in cancer patients. He is currently evaluating this vaccine in combination with an approved immunotherapy—pembrolizumab— to help boost patients' immune responses against the cancer. His latest research explores the role of immunity and inflammation in the development of lung cancer at its earliest stages in the context of pulmonary premalignancy. Dr. Dubinett has served in many leadership roles for the early detection and immunobiology of lung cancer. His research has been supported by VA Merit Review research funding for the past thirty years. He is a funded member of the National Cancer Institute's Early Detection Research Network. He serves as a Principal Investigator in the Moonshot Program Human Tumor Atlas Network as well as the Stand Up to Cancer Dream Team for lung cancer interception. He is chief of the division of pulmonary and critical care medicine at the University of California, Los Angeles, and director of the UCLA Lung Cancer Research Program. His career exemplifies how basic research performed in his laboratory has informed his clinical trial work which is expected to have a real-world impact on the treatment of lung cancer in the Veteran population.
Michael R. Zile, M.D., at the Ralph H. Johnson VA Medical Center, was awarded the 2019 Middleton Award in recognition of his ground-breaking contributions to the field of Cardiology. His basic to translational studies have helped to identify new therapeutic targets for clinical trials aimed at regulating left ventricular structure and function in patients with heart failure and a preserved ejection fraction. Dr. Zile is an internationally recognized expert in the field of heart failure with a preserved ejection fraction (HFpEF), the largest unmet need in modern Cardiology. He is credited with (i) formulating the criteria used to clinically identify the phenotype of patients with HFpEF, which have been established and adopted by heart failure guidelines; (ii) developing predictive/prognostic assessment of morbidity and mortality in HFpEF patients, which has achieved a clinically relevant level of accuracy; (iii) advancing novel mechanisms of disease that are beginning to be targeted for clinical drug development; and (iv) clinical trial study designs that are being optimized for evaluating drug, cell, and device management of HFpEF.
William A. Banks, M.D., of the VA Puget Sound Health Care System, was the recipient of the 2018 Middleton Award in recognition of his seminal contributions to the field of neuroimmunology. Dr. Banks contributed to the paradigm shift in our understanding of how peptides cross the blood-brain barrier (BBB) to modify brain function and how the BBB facilitates brain-peripheral tissue communication. He is a leading expert on the BBB and how deregulation of peripheral homeostatic mechanisms contributes to the development of neuropathological disorders. Dr. Banks is responsible for several pivotal advances in neuroimmunology, which have important clinical ramifications. His important discoveries include: (i) the polarized secretion of cytokines by brain endothelial cells of the BBB and their effect on cognition; (ii) the ability of gastrointestinal hormones to cross the BBB and how leptin transport across the BBB is impaired in obesity; (iii) that inflammation results in decreased blood-to-brain transport of amyloid-beta peptide, leading to its accumulation and promotion of the Alzheimer's disease phenotype; (iv) how excess glucose metabolism in diabetes results in pericyte death and BBB disruption; and (v) how HIV-1 as free virus crosses the BBB by binding to the mannose-6-phosphate receptor and elucidating those controlling mechanisms. These discoveries have inspired Dr. Banks, in collaboration with colleagues, to develop peptide analogs with improved central nervous system (CNS) availability e.g. breaker peptides that remove amyloid plaque from the brain; peptides that protect CA1 hippocampal neurons from ischemic stroke; and antisense oligonucleotides that decrease brain levels of amyloid beta peptide and improve cognition in pre-clinical animal models. The discoveries by Dr. Banks have firmly contributed to the establishment of the field of neuroimmunology and have promoted the discovery of many neurotherapeutics. His foundational work on the BBB has had a broad impact on the healthcare of Veterans.
The 2017 Middleton Award was awarded to two candidates: Robert A. Bonomo, M.D. from the Louis Stokes Cleveland VA Medical Center and H. Kirk Hammond, M.D. from the San Diego Healthcare System.
Robert A. Bonomo, M.D., of the Louis Stokes Cleveland VA Medical Center, was the recipient of the 2017 Middleton Award in recognition of his seminal contributions to the epidemiology, pathogenesis, diagnosis, prevention, and treatment of multidrug resistant infections. Dr. Bonomo is a nationally and internationally recognized expert in the field of antibiotic resistance research. His basic science studies have focused on the mechanisms and epidemiology of antibiotic resistance in Gram-negative bacteria with a major focus on the molecular determinants of beta-lactam action and resistance. His investigative activities include susceptibility testing, genetics and mutagenesis, genomics, molecular epidemiology, protein engineering, steady and pre-steady state kinetics, drug discovery, structural biology/X-ray crystallography, spectroscopy and proteomics. His research has involved translating fundamental discoveries and the evaluation of novel pharmaceuticals and molecular diagnostics to the clinic. His pivotal paper describing the spread of multidrug resistant Acinetobacter within Walter Reed Hospital in 2006 alerted the medical community to the challenges associated with Veterans who had served in the Middle East. Dr. Bonomo's research is of great importance to the VA and the general population, as bacterial resistance accounts for more than 30,000 deaths annually.
H. Kirk Hammond, M.D., of the San Diego Healthcare System, was awarded the 2017 Middleton Award in recognition of his pioneering contributions to our understanding of the pathophysiologic mechanisms underlying cardiovascular dysfunction and the means by which cardiac function can be improved using gene therapy approaches. Dr. Hammond is responsible for several seminal advances in cardiology, which have translated into important clinical advances. His research in preclinical heart failure models has served as the basis for the first double-blinded randomized Phase 2 gene therapy trial for patients with heart disease. Two additional late stage clinical gene therapy trials include: (i) a Phase 3 trial of AC6 gene transfer for clinical heart failure; and (ii) a Phase 3 trial of FGF-4 (an angiogenic gene) for angina. If successful, these trials could lead to the first registration of a gene therapy product for treating heart disease. Dr. Hammondâ€™s recent work in insulin-resistant mice showed that a one-time intravenous injection of an AAV vector encoding urocortin 2 restores insulin sensitivity, suggesting a potential therapy for clinical type-2 diabetes. Dr. Hammond is a pioneer of intracoronary gene transfer and novel gene therapy approaches that will have a broad impact on the clinical care of Veterans and others with cardiovascular diseases.
The 2016 Middleton Award was awarded to two candidates: Stavros C. Manolagas, M.D., Ph.D., of the Central Arkansas Veterans Healthcare System and Ann Richmond, Ph.D., from the Tennessee Valley Healthcare System.
Stavros C. Manolagas, M.D., Ph.D., of the Central Arkansas Veterans Healthcare System, was the recipient of the 2016 Middleton Award in recognition of his ground-breaking contributions to our knowledge of the pathophysiologic mechanisms underlying osteoporosis and other metabolic bone diseases. Dr. Manolagas is responsible for several seminal advances in skeletal biology that have translated into important clinical treatments. His discoveries have contributed to the improved management of chronic kidney disease by the administration of the active form of Vitamin D to reduce secondary hyperparathyroidism. His other landmark contributions include understanding the role of estrogen and androgen in bone biology and the pathophysiology of osteoporosis in women and men. His pioneering work on the mechanisms responsible for the loss of bone following estrogen or androgen deficiency accelerated the development of a targeted antibody to RANKL, a new class of therapeutics, as a treatment of osteoporosis and painful metastatic bone diseases. His research also helped to explain the resulting skeletal frailty during glucocorticoid treatment; the bone loss which occurs with immobilization; and the pivotal role of oxidative stress in the osteoporosis of aging in both sexes. Dr. Manolagas' work is notable for its originality both from a conceptual and technical standpoint
Ann Richmond, Ph.D., of the Tennessee Valley Healthcare System, was awarded the 2016 Middleton Award in recognition of her pioneering work in the field of cytokine biology, which has important translational applications in vascular biology and the treatment of melanoma, breast cancer and other tumors. Dr. Richmond and her team purified, cloned and characterized one of the first known chemokines, CXCL1/MGSA. She and her collaborators were the first to show that the receptor for this chemokine, CXCR2, is a mediator of wound healing, angiogenesis, and tumor growth. These seminal findings led to the understanding that tumor cell production of chemokines can impact the recruitment of immune cells as well as endothelial cells to the tumor to promote angiogenesis, inflammation, and tumor growth. Additional findings from her basic science research have formed the basis for the design of future clinical trials combining targeted therapies and immunotherapy for melanoma and breast cancer malignancies. Dr. Richmond's highly translational research in precision medicine and tumor immunology will have a broad impact on the healthcare of Veterans.
Raymond F. Schinazi, Ph.D., D.Sc. (Hon.), from the Atlanta Veterans Affairs Medical Center, was awarded the 2015 Middleton Award for his landmark contributions to medicinal chemistry and virology. Dr. Schinazi is recognized for his pioneering work in the development of novel antiviral drugs that now form the backbone of combination treatment regimens for human immunodeficiency virus (HIV) infection. The efficacy and safety of these medications have had a profound and transformative impact on the course of the acquired immune deficiency syndrome (AIDS) epidemic, changing HIV infection from a death sentence into a manageable chronic illness. Additionally, Dr. Schinazi’s pioneering research led to the development of a curative treatment for hepatitis C virus (HCV) infected patients now in widespread use. He has been described as a visionary scientist who “ranks alongside scientists such as Maurice Hillemann and Jonas Salk in terms of the impact of his inventions have had on infectious diseases.” His antiviral drugs have not only benefited the VA patient population immensely but have saved millions of lives worldwide.
Yvette Taché, Ph.D., from the VA Greater Los Angeles Healthcare System, was awarded the 2014 Middleton Award for her seminal contributions to our understanding of central nervous system (CNS) control of peripheral autonomic pathways that influence gastrointestinal function. Her research is focused on clinical disorders of stress-related autonomic dysfunction including posttraumatic stress disorder and so called "functional disorders" such as irritable bowel syndrome (IBS), diarrhea, constipation, abdominal pain, and gastroparesis. These disorders are major causes of morbidity in the Veterans, as well as the general population. Her studies have made fundamental contributions to the understanding of the chemical transmission between CNS neurons and peripheral autonomic pathways, and she has been a key leader in the development of the relatively new field of neuro-gastroenterology. Her work has also translated the knowledge of these brain-gut pathways to experimental models of clinical disorders such as IBS and the development of treatment approaches for a number of stress related gastrointestinal functional disorders.
The 2013 Middleton Award was awarded to two candidates: Dale N. Gerding, M.D., from the Edward Hines, Jr. VA Hospital, Hines, IL and Raj K. Goyal, M.D., from the VA Boston Healthcare System, Boston, MA.
Dale Gerding, M.D., from the Edward Hines Jr. VA Hospital, was awarded the 2013 Middleton Award for his significant contributions to the epidemiology, pathogenesis, diagnosis, and treatment of Clostridium difficile colitis, a major problem in the VA system and worldwide. Dr. Gerding designed the first prospective, randomized trial of oral metronidazole and vancomycin, which showed no significant difference in clinical outcome and led to considerable cost savings. He established that recurrences in infection were caused by new strains of C. difficile, and he documented clindamycin resistance in C. difficile. He also pioneered the development of a potential preventative strategy of colonizing patients with a non-toxigenic strain of C. difficile, which is now in clinical trials. Dr. Gerding's long and distinguished career in the VA is internationally recognized for his landmark contributions to antibiotic pharmacokinetics, hospital epidemiology, and most prominently, C. difficile colitis.
Raj Goyal, M.D. from the VA Boston Healthcare System was awarded the 2013 Middleton Award for his seminal contributions to the field of gastroenterology that led to important advances in our understanding of esophageal and gastric physiology and clinical disorders including Barrett's esophagus, gastroesophageal reflux disease (GERD), diffuse esophageal spasm, esophageal pain, and gastroparesis. He provided the first evidence of the existence of multiple muscarinic receptor subtypes in the gut and the influence of vagal innervation, transmitters and peptides in the regulation of lower esophageal sphincter muscles. Importantly, his studies on esophageal sensory neurophysiology represented the early investigations that opened the field of visceral nociception in the gut. Dr. Goyal's research changed the course of our understanding of structure and function of the gastrointestinal enteric nervous system and motility. He is considered as one of the fathers of the field of gastrointestinal motility.
Robert Farese, M.D., from the Tampa VA Medical Center was awarded the 2012 Middleton Award in recognition of his scientific contributions to the field of endocrinology that led to a better understanding of insulin action in normal conditions and states of obesity, metabolic syndrome, and type 2 diabetes and to the development of a new class of therapeutic agents for treating these clinical disorders. Throughout his career, he has been at the forefront of important research studies on basic intracellular phospholipid- and protein kinase-dependent signaling systems, particularly as related to the mechanism of action of insulin and deficiencies thereof in clinically important states of obesity and type 2 diabetes mellitus. He is responsible for opening up the avenues of exploring lipid mediators and atypical protein kinase C (aPKC) in insulin action. This has had a tremendous impact on the thinking about the underlying abnormalities in type 2 diabetes and in the development of new therapeutic approaches for diabetes based on small molecule aPKC inhibitors.
Fred Finkelman, M.D., from the Cincinnati VA Medical Center was awarded the 2011 Middleton Award for his pioneering work in the field of immunology and host-pathogen interactions. He has contributed to our understanding of the role of cytokines in immune-mediated disease, the mechanisms of host defense in parasitic infection, the role of dendritic cells in antigen presentation, the mechanism of allergy, and technical innovations to measure cytokine production in vivo. Dr. Finkelman's work can be found at the heart of many innovative therapies for allergy and vaccine development. He was the first to demonstrate the role of Immunoglobulin D in Î² cell signaling and the role of cytokines in isotype switching. He published the initial paper on antigen presentation by dendritic cells and he demonstrated the role of different cytokines and the contributions of Immunoglobulin G and Immunoglobulin E to asthma and anaphylaxis. He also made profound contributions to the field of immunoparasitology.
The 2010 Middleton Award was awarded to two candidates: Jerome Siegel, Ph.D., from the VA Greater Los Angeles Healthcare System, and Joe Brice Weinberg, M.D., from the Durham VA Medical Center.
Jerome Siegel, Ph.D., of the VA Greater Los Angeles Healthcare System was awarded the 2010 Middleton Award in recognition of several areas, including discovering the mechanism of rapid eye movement (REM) sleep, and discovering that the cause of narcolepsy as well as a crucial component of Parkinson's disease is due to loss of hypocretin neurons. Dr. Siegel's work is commendable in its innovativeness and creativity. His methodologies and novel sleep studies resulted in the improved understanding of not only the mechanisms of REM sleep, but also in the very function and evolutionary significance of sleep. This work has resulted in improved treatments for sleep disorders, including the use of hypocretin-1 to treat narcolepsy. His work has had high scientific impact in the treatment of diseases affecting Veterans and patients worldwide.
Joe Brice Weinberg, M.D., of the Durham VA Medical Center was awarded the 2010 Middleton Award in recognition of his contributions to our understanding of resistance to infections, pathways of inflammation, and regulation of normal and leukemic blood cells. His discovery that monocytes can be infected by HIV led to a breakthrough in understanding the pathobiology of the virus. His discovery of the role of nitric oxide and its metabolites in malaria infections led to clinical trials of arginine, which increases NO levels, as a treatment for malaria. He has been a force of innovation and paradigm change in the field of immunology for the past three decades through his research, leadership, and mentorship. Dr. Weinberg's career and scientific contributions have had and will continue to have a high scientific impact in areas involving Veterans and patients worldwide.
The 2009 Middleton Award was awarded to two candidates: Michael D. Norenberg, M.D., from the VA Miami Healthcare System, and Edward Weinman, M.D., from the VA Maryland Healthcare System in Baltimore.
Michael D. Norenberg, M.D., of the VA Miami Healthcare System was awarded the 2009 Middleton Award for his contributions and understanding that the glial cell biology was an essential part of understanding neurological function and dysfunction. His studies showed that hepatic encephalopathy was primarily a result of astrocyte dysfunction. He alone proved that central pontine myelinosis (CPM) is caused by a rapid correction of hyponatremia (a sodium imbalance), rather than hyponatremia itself. Because of Dr. Norenberg's research and work in this area, he has rapidly transformed the standard therapy for hyponatremia and CPM has consequently become a rarely observed condition in clinical practice today.
Edward Weinman, M.D., of the VA Maryland Healthcare System in Baltimore was awarded the 2009 Middleton Award for his outstanding contribution to our understanding of kidney function, from mapping out the molecular processes to discovering a new family of proteins called NHERF. He showed that these proteins are what regulate kidney functions and demonstrated their function in an animal model. His discovery has impacted not only the clinical relevance of the kidney, but also clinical syndromes in other disparate organ systems such as the gastro-intestinal tract and neurologic systems. Dr. Weinman's scientific contributions will have a widespread impact on the clinical care of Veterans and the general population.
The 2008 Middleton Award was presented to Stephen G. Waxman, M.D., Ph.D., form the VA Connecticut Healthcare System at West Haven. Dr. Waxman exemplifies the bridge between science and medicine. He has worked in the Department of Veterans Affairs since 1978. He is the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University, and has served as Chairman of Neurology at Yale since 1986. In 1986, he established the Neuroscience and Regeneration Research Center, a collaboration of the Department of Veterans Affairs, Yale University, and the Paralyzed Veterans of America. Prior to moving to VA Connecticut and Yale, Dr. Waxman worked at Harvard, MIT, and Stanford. He has published more than 500 scientific papers, authored the book Spinal Cord Compression, and has edited eight books. He has trained hundreds of neurologists and neuroscientists. Dr. Waxman's research builds upon the "genomic revolution," to develop new strategies for promoting restoration of function after spinal cord, nerve, and brain injury. His honors include the NIH Tuve Award, the Albert Einstein College of Medicine Distinguished Alumnus Award, and the American Academy of Neurology Dystel Prize and Wartenberg Award, and he is a member of the National Academy of Sciences' Institute of Medicine.
The 2007 Middleton Award was awarded to two candidates: Robert Freedman, M.D., from the Denver VAMC, and Daryl K. Granner, M.D., from the Nashville VAMC.
Robert Freedman, M.D., received the 2007 Middleton Award in recognition of his contributions to understanding of the causes and treatment of schizophrenia, a major cause of morbidity in the VA. Not only has he opened doors in our understanding of the role of the nicotinic receptor in P50 gating and schizophrenia, but his paradigm of moving from the molecular neurobiological level, to genetic studies to treatment is a paradigm that has set a precedent for the field. His more recent studies with an alpha-7 nicotinic agonist, DXMB-A, hold the potential promise of a new treatment option for schizophrenia distinct from the more conventional approach of the dopamine antagonists. Dr. Freedman's findings have a broad impact on the clinical care of Veterans and the population at large.
Daryl K. Granner, M.D., was awarded the Middleton Award, 2007, for his discovery of insulin action in diabetes. Dr. Granner was the first to show that insulin regulated gene expression, with a focus on the PEPCK gene. Since this seminal discovery, insulin has been shown to regulate the expression of multiple genes, and is now considered one of the major actions of insulin and important in the development of Type 2 diabetes and other conditions related to Type 2 diabetes. His findings have led to an extension of diabetes related abnormalities to pre-diabetic conditions including the metabolic syndrome, which in turn includes the development of cardiovascular disease in patients who do not have overt diabetes. Dr. Granner's findings have had a broad impact on the clinical care of Veterans and the population at large.
The 2006 Middleton Award was awarded to two candidates: Roland C. Blantz, M.D., from the VA San Diego Healthcare System and Michael W. Weiner, M.D., from the San Francisco VA Medical Center.
Dr. Blantz's scientific contributions are enormous and include a large spectrum of studies related to renal physiology and pathophysiology. He was the first to discover the mechanism by which angiotensin II decreases glomerular filtration, the role of renal nerves, and mechanisms of renal regulation through the tubuloglomerular feedback. He is recognized as a world expert in renal physiology and mechanisms of renal disease. His work laid the foundation for clinical studies establishing the role of the renin angiotensin system in progression of renal disease and paved way for new therapeutics. More recently his work has established the link between renal disease and diabetes. He has been a continuously funded VA investigator with national and international reputation.
Dr. Weiner has been a leader in the field of MRI & MRS brain imaging in neurodegenerative disorders for more than two decades. This is an area of high importance in general, as our population ages, as well as to the VA research mission, in particular. In addition, Dr. Weiner has worked in PTSD and Gulf War Illness, both of which have particularly high significance to the VA mission. That Dr. Weiner's work has emphasized the advancement of neuroimaging is also of high significance. Brain imaging is one of the fastest growing and highest impact areas of research, in close competition with genetics/genomics for overall scientific impact. Dr. Weiner's work has done a great deal to advance the use of these important techniques in the clinical neurosciences.
Thomas D. Bird, M.D., of the VA Puget Sound Healthcare System, Seattle, WA, was awarded the 2006 Middleton Award in recognition of his contributions towards our understanding of the genetic bases of neurodegenerative disorders. His work led to the discovery of important genetic mutations involved in major neurodegenerative diseases, notably Alzheimer's Disease (AD) and frontal temporal dementia. The identification of presenilin mutations has been used to create more useful models for AD research, which have proven critical for drug discovery in the amyloid biology field. Dr. Bird's research has also led to discovery of mutations in tau in a subset of frontal temporal dementia. This has also led to the development of animal and cell culture models that, with these mutations, have provided the first, and still the best, models for tangle pathology. With these models, a new arena of drug discovery for AD has been developed. The impact of Dr. Bird's work continues to be substantial and will continue to contribute to the development of new anti-tangle treatments for dementias, a major healthcare problem relevant to the VA as well as the general population.
John C. Crabbe, Ph.D., of the Portland VAMC was awarded the 2004 Middleton Award for his contributions towards our understanding of the genetic bases and behavioral consequences of ethanol intake (e.g., withdrawal and tolerance). His work with animal models of alcoholism has advanced the field of behavioral genetics, and it has important implications for showing the complexity of analogous traits or phenotypes underlying alcohol drinking behavior and alcoholism in humans. He demonstrated that alcohol tolerance, alcohol dependence and alcohol preference are distinct processes that can be dissected genetically. He has also shown that there is a common genetic mechanism for developing dependence on various drugs of abuse (e.g., alcohol, barbiturates, benzodiapenes, and nitrous oxide). His studies have the promise of identifying neural systems affected by protective genes as well as genes that promote risk for development of alcohol and drug dependence. In turn, effective pharmacological and environmental therapies can then be identified for treating addictions.
Andrew H. Kang, M.D., of the Memphis VAMC was awarded the 2003 Middleton Award in recognition of his outstanding body of work that continues to impact our understanding and treatment of connective tissue diseases, particularly rheumatoid arthritis. His original and seminal contribution was the discovery and development of the collagen-induced arthritis (CIA) rodent model of chronic arthritis. The CIA model was the first to prove that immunization with an autologous cartilage component could lead to inflammatory, autoimmune arthritis. His work with the animal model also resulted in the development of several potential immunotherapies and vaccines that could prevent the development of CIA. More recently, he has engineered analog peptides that prevent the development of CIA in the animal model. Some of these peptides were used in clinical trials.
Douglas D. Richman, M.D., of VA San Diego Healthcare System was awarded the 2002 Middleton Award for his research on HIV and AIDS that helped guide treatment for millions of patients worldwide Dr. Richman is noted for his studies on azidothymidine (AZT), the first drug approved in the United States to treat HIV. He and his colleagues established the effectiveness of the drug in the 1980s. Later, studies by Dr. Richman revealed the emergence of AZT-resistant strains of HIV. The appreciation of the importance of HIV drug resistance studies and his pioneering studies on combination drug therapy led to the development in the 1990s of the highly active antiretroviral therapy (HAART). More recently, Dr. Richman has shown that HAART does not completely eradicate HIV, but leaves small reservoirs of HIV in immune cells, even when blood tests show no trace of the virus. Amid these findings, he is at the forefront of efforts to study neutralizing antibodies to HIV, which may be of importance in the development of an AIDS vaccine.
Eugene C. Butcher, M.D., of the VA Palo Alto Healthcare System was awarded the 2001 Middleton Award in recognition of his contributions to the field of immunology, particularly his research on the fundamental processes of immune response and inflammation processes of numerous diseases that affect Veterans. Dr. Butcher's work has stimulated and broken new ground in understanding the molecular basis of lymphocyte homing. He identified critical molecules and established the unique homing receptor-ligands for lymphocyte trafficking into and out of the mucosal immune system of the gastrointestinal tract. He also showed that treatment of mice with monoclonal antibodies alpha4 and beta7 block T-cell mediated inflammatory bowel disease, clearly demonstrating the role of these mucosal homing pathways in immunity and inflammation.
Edward R. Block, M.D., of the Malcolm Randall VA Medical Center in Gainesville, Florida, received the 1999 Middleton Award in recognition of his achievements in the field of pulmonary and critical care medicine. He was among the first to identify and characterize the metabolic functions of lung endothelial cells, leading to a re-evaluation of their role in normal and abnormal lung biology. He subsequently worked on the mechanisms by which oxidant injury affects the metabolic functions of the lung endothelial cells, leading to an understanding of how lung endothelial cell injury leads to acute and chronic manifestations and patho-physiology of lung disease. Dr. Block's work provided the basic science infrastructure for the clinical use of metabolic functions of the lung as indices of pulmonary injury, and for the use of supplemental L-arginine in the treatment of pulmonary vascular dysfunction associated with acute and chronic lung injuries.
Robert W. McCarley, M.D., of the Brocton/West Roxbury VA Medical Center was awarded the 1998 Middleton Award for his contributions to research on sleep and the neurophysiology of behavior. He was the first to systematically develop quantitative measures to test hypotheses on the cellular control of sleep states. He and his colleagues reported important control mechanisms for the rapid eye movement (REM) state and the non REM state of sleep. These studies set the stage for new approaches to treating sleep abnormalities, including sleep disruptions in psychiatric and other disorders. Dr. McCarley also made important advances in understanding the basic biology of schizophrenia, a devastating mental illness affecting many Veterans. His studies are focused on teasing out brain abnormalities that produce the behavioral symptoms of the disorder.
A world leader in the study of alcoholism, Marc A. Schuckit, M.D., of the VA San Diego Healthcare System, was honored with the 1997 Middleton Award for his scientific contributions to the field of alcoholism and drug addiction. Of particular note were his studies showing the importance of genetic influences in alcohol dependence. His innovative population studies set the stage for exciting progress now being made in research to identify genes that play a role in alcoholism. His other major contribution was establishing the relationship between alcohol or drug dependence and severe psychiatric syndromes. He also focused on the treatment of psychiatric problems and the evaluations of the potential importance of separate tracks of care for people dependent on specific types of drugs.
A world-renowned leader in the fields of diabetes and metabolism, Daniel Porte, Jr., M.D., of the Seattle VA Medical Center was honored with the 1996 Middleton Award for his contributions to the field of diabetes. His pivotal observations form the foundation for our current understanding of the neural control of the pancreatic islet cells. He is most recognized for his contributions to our understanding of the role of pancreatic beta-cell dysfunction in the hyperglycemia of non-insulin dependent diabetes. He and his colleagues defined the separate but interactive roles of insulin secretion, insulin sensitivity, and glucose effectiveness in controlling glucose tolerance- all three now recognized to be abnormal in non-insulin dependent diabetes. Dr. Porte was the first to propose that insulin regulates body weight by acting on the brain. He demonstrated the presence of insulin receptors in specific regions of the central nervous system and showed that insulin directly affects neuropeptide y, a potent stimulator of food intake.
Gerald F. DiBona, M.D., of the Iowa City VA Medical Center was awarded the 1995 Middleton Award for his internationally recognized contributions to renal and cardiovascular medicine. His research focuses on the neural control of kidney function. He showed that increased nerve activity affected the kidney's ability to filter impurities from the blood, regulate blood flow and control sodium and water retention. As a result, the body retains more sodium and water than normal, and swelling occurs in various parts of the body. Dr. DiBona's work led to the development of possible treatments that work along the entire pathway between the brain and the kidney.