Clarke Tankersley, PhD, ScM

Clarke Tankersley received his PhD from Pennsylvania State University in 1991 and his ScM from Johns Hopkins University in 1988. He focuses his research attention on the control of ventilation and how genetic predisposition may facilitate individual susceptibility to airborne toxins. These interests emphasize the identification of specific major and modifying genes that determine normal breathing pattern and the control of ventilation during hypercapnic and hypoxic exposures. The strength and success of this research endeavor is found in the unique, multidisciplinary approach utilizing inbred murine strains to model physiological systems affected by heredity in human populations. For example, these experiences have led us to better understand the changes in respiratory function associated with amyotrophic lateral sclerosis (ALS). Dr. Tankersley's training is consistent with an integrated systems physiological approach, and his educational scope is comprised of topics concerning aging and environmental stress as these pertain to cardiovascular, reproductive, and thermoregulatory mechanisms in humans. His career goals also include a strong commitment to teaching and directly interacting with graduate, undergraduate honors, and minority underrepresented students. In addition, he is dedicated to collaborating with research associates and other community professionals.

Robert Brown, MD, MPH

Robert Brown's overall area of research interest is the structure-function relationship of pulmonary airways and vessels and how they relate to reactive airway disease. Current research interests include high-resolution computed tomography of the pulmonary airways and vessels in vivo in order to study the following: (1) regional differences in airways constriction in response to a variety of differential bronchoconstrictors, (2) location and mechanism of inhalational-induced bronchodilation, (3) effects of various physiologic stimuli on airway constriction, (4) pulmonary vasculature and airway interaction following various physiologic stimuli, and (5) 3-D reconstruction of the airway tree.

Brendan Canning, PhD

Brendan Canning is an associate professor of medicine at The Johns Hopkins Asthma and Allergy Center. He received his PhD in physiology from The Johns Hopkins University in 1993. After postdoctoral fellowships at Hopkins and in Germany, Dr. Canning joined the faculty at the Asthma and Allergy Center in 1996. His research is focused on the neural regulation of the airways.

Robert Frank, MD

Robert Frank's early research on the mechanical properties of the lung has come to focus on interactions between the lung and pollutant gases and particles—i.e., the biological factors of the lungs and the physicochemical properties of the pollutants—to understand governing regional dose, response, and the variability of response, or susceptibility, among healthy individuals and those with underlying respiratory disorders.

He has served as a member of the EPA's Science Advisory Board and on the Clean Air Sciences Advisory Committee. The latter is mandated by the Clean Air Act to review all criteria developed by the Agency to establish or revise national ambient air quality standards.

Bernard G. Jaar, MD, MPH

Bernard Jaar, a member of the Division of Nephrology at the School of Medicine, is a physician who specializes in kidney disease. He earned his MD from the State University of Haiti and completed his internal medicine and nephrology training in Paris. In the United States he completed his internal medicine residency at the Graduate Hospital in Philadelphia and his nephrology fellowship at the Johns Hopkins Hospital. His research interest is in the conduct of epidemiologic studies in the field of end-stage renal disease and its complications.

Dr. Jaar has published numerous articles and has received much recognition for his work, including the Boehringer Mannheim Prize for his research on human recombinant erythropoietin, the Victoria Prize (awarded by the Collège de Médecine to foreign physicians trained in France), and the Ruth L. Kirschstein National Research Service Award to train in renal disease epidemiology. In 2003 he received the School of Medicine’s Richard Ross Clinician Scientist Award.

Thomas Kensler, PhD, AB

Thomas Kensler's research interests focus on the biochemical and molecular mechanisms involved in the induction of cancer by chemicals to serve as a basis for the prevention, interruption, or reversal of these processes in man. One of the major mechanisms of chemical protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly Phase 2 enzymes such as glutathione S-transferases, UDP-glucuronosyl transferases, and NAD(P)H:quinone reductase. Furthermore, animal studies indicate that induction of Phase 2 enzymes is a sufficient condition for obtaining chemoprevention and can be achieved in many target tissues by administering any of a diverse array of naturally occurring and synthetic chemical agents. Dr. Kensler's work utilizes animal and cell culture models to elucidate mechanisms of inhibition of aflatoxin hepatocarcinogenesis by dithiolethiones such as oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithole-3-thione]. While induction of glutathione S-transferases clearly plays an important role in chemoprevention of aflatoxin hepatocarcinogenesis, ongoing studies are seeking to identify additional induced genes. cDNAs for several novel as well as unexpected genes have been isolated, several of which are involved in attenuating oxidative stress and inflammation. Their contributions to protection against carcinogenesis are under investigation. Studies are also underway to elucidate the role of Nrf2 and other transcription factors in mediating enzyme induction by chemopreventive agents.

Raymond Koehler, PhD

Raymond C. Koehler is a cardiovascular physiologist and a neuroscientist. He performed his undergraduate work in electrical engineering at Rensselaer Polytechnic Institute in Troy, New York (1970), his graduate work in cardiovascular physiology at the State University of New York at Buffalo (1978), and his postdoctoral training in cerebrovascular physiology in the Department of Environmental Health Sciences at the Johns Hopkins University School of Public Health. In 1980, he joined the faculty in the Department of Anesthesiology at the School of Medicine, where he is currently a professor with a joint appointment in the Department of Environmental Health Sciences. Dr. Koehler's areas of research include regulation of cerebral circulation, mechanisms linking cerebral blood flow to neural activation, and hemoglobin-based oxygen carriers as blood substitutes. His research also extends to investigating the mechanisms of brain injury arising from stroke, cardiac arrest and resuscitation, and hepatic encephalopathy. Dr. Koehler is a past associate editor of the American Journal of Physiology: Heart and Circulatory Physiology and currently serves on the editorial board of the American Heart Association journal, Stroke.

Wayne Mitzner, PhD, MS, BS

Wayne Mitzner's research is focused on the relation between lung structure and airway function. Ongoing experiments in several animal models (mice) take advantage of direct visualization of airways in vivo using high-resolution computed tomography. Dr. Mitzner studies both basic pathophysiologic mechanisms and the effect of allergens and other air pollutants on the airways. With such imaging, he can directly determine the effect of airway wall thickening due to inflammation or edema, increased airway smooth muscle contraction, and their interaction in vivo. In another area of ongoing research, he has recently developed a unique model of angiogenesis in the murine lung. Using this model, he is attempting to isolate specific genes and gene products that regulate this important process.

Sekhar Reddy, PhD, MSc

Sekhar Reddy's lab research primarily focuses on elucidating the molecular mechanisms underlying environmental toxin–induced respiratory pathogenesis, including lung cancer.

Dr. Reddy's lab studies primarily focus on the molecular mechanisms underlying cigarette smoke–induced respiratory pathogenesis. Squamous cell metaplasia and hyperplasia of airway epithelium have been considered to be among the pre-neoplastic stages that may lead to bronchogenic cancer. Recently, he has shown that the c-Jun:Fra-1-based activator protein 1 (AP-1) complex plays a critical role in tumor promoter and cigarette smoke–induced expression of the squamous differentiation marker, SPRR1B, in bronchial epithelial cells. AP-1 acts as one of the environmental biosensors that participate in cellular switching of the genetic program in response to various toxic and mitogenic stimuli. However, the physiological relevance and specific contribution of individual AP-1 family members to lung biology and toxicant-induced respiratory pathogenesis remain enigmatic. Emerging evidence indicates that Fra-1 plays a key role in pulmonary defense, injury, and repair processes, as well as tumor progression. Fra-1 is not only over-expressed in a wide variety of tumors and malignant cells but also causally linked to the up-regulation of genes associated with tumor progression and invasiveness. Currently, he is elucidating both transcriptional and signal transduction pathways regulating the induction of Fra-1 by various toxicants, including cigarette smoke. Also, transgenic mouse models are being used to better understand the functional role of Fra-1 in lung injury, repair, and cellular transformation. These studies may lead to the development of novel treatment strategies against toxicant-induced respiratory pathogenesis.

Kellogg Schwab, PhD, MS

Kellogg Schwab is actively involved in the Center for Water and Health at the Johns Hopkins University. The goal of the Center is to integrate Hopkins researchers from multiple disciplines to address water-related public health issues. Dr. Schwab's overall research focus is the development of new approaches to evaluate human microbial exposure assessment and to investigate the fate and transport of agents in the environment. His laboratory uses classical microbiology in conjunction with advanced molecular techniques, including quantitative polymerase chain reaction, internal standard controls, and proteomics, in both laboratory and field-based research projects. Data gathered during these studies are then integrated into exposure assessment and risk analysis.

Current research projects involve improving environmental detection methods for noroviruses and investigating how many important human pathogens, including noroviruses, hepatitis A virus, rotaviruses, antibiotic-resistant Campylobacter, antibiotic-resistant enterococci, Cryptosporidium parvum, Toxoplasma gondii, and Aspergillus persist and are transported through environmental media (water, air, and food). In collaboration with the Centers for Disease Control and state health laboratories, he has investigated numerous waterborne and foodborne outbreaks of viral gastroenteritis. Other projects include investigating the use of better microbial water quality indicators, such as bacteriophages, for rapid, cost-effective determination of microbial water quality; working on improvements for drinking-water and wastewater treatment processes by assessing the microbial removal efficiency of micro- and ultrafiltration units, as well as full-scale riverbank filtration systems; assessing the impact of concentrated animal feeding operations on human health, the environment, and quality of life in the communities in which these operations are located; and evaluating the impact of human pollution on urban streams and the Chesapeake Bay caused by aging and deteriorating distribution systems by combining microbial, chemical, and geographic information system (GIS) data.

Machiko Shirahata, MD, DMSc

Machiko Shirahata's research goal is to understand the hypoxic chemosensing mechanisms of the carotid body and to explore how the function of the carotid body is involved in physiology and pathophysiology of the cardiopulmonary and autonomic nervous systems. Many studies have suggested that carotid body function is closely correlated with common human diseases. For example, obstructive sleep apnea ia a major health problem in the United States. Approximately 4 percent of the population in any age group are affected. Hypertension and other cardiovascular diseases are major consequences in this syndrome. The excitation of the carotid body during apnea is an immediate cause of nocturnal hypertension. At the same time, the excitation of the carotid body is essential to arouse these patients and to terminate apnea. In borderline cases of hypertension or in mild hypertensive subjects, the stimulation of the carotid body causes over-excitation of the sympathetic nervous system. On the other hand, patients who have suffered near-fatal asthma attacks demonstrated a marked reduction in the function of the carotid body. Finally, in some rare diseases, such as congenital hypoventilation syndrome and sudden infant death syndrome, anatomical and biochemical abnormalities of the carotid body have been shown.

Dr. Shirahata's hypothesis of chemoreception of the carotid body is that nicotinic ACh receptors in the carotid body are sensitive to oxygen tension. Hypoxia increases the sensitivity of the receptor to ACh and enhances the effect of ACh. Since ACh is an excitatory neurotransmitter in the carotid body, the sensitization of the receptor by hypoxia increases neural discharges in the sensory afferent nerves from the carotid body. Her research team is investigating underlying mechanisms of hypoxic sensitivity of nicotinic receptors using multidisciplinary approaches with patch clamp, microfluorometric, immunocytochemical, and molecular biological techniques.

Ernst Wm. Spannhake, PhD, MS, BS

Inflammation is recognized as an essential element of many airway pathologies, and Ernst Spannhake's recent research has focused on the role of the epithelium in this inflammatory process. These studies use human in vivo and cell culture approaches to probe the mechanisms through which epithelial pro-inflammatory activity is initiated and modulated. Pro-inflammatory processes of interest include (1) the induction of mediator synthesis and release, (2) the modulation of epithelial barrier function, (3) the expression of cell-surface markers of inflammation and cell adherence, and (4) epithelial activation of T lymphocytes via MHC class I and II receptors and accessory molecules. Investigations carried out in normal and allergic asthmatic individuals undergoing controlled exposures are used to link in vitro cellular data with observations made in human subjects.

Current areas of research interest include (1) the role of bronchial epithelial cells in the modulation of T lymphocyte activity during respiratory virus infection and the role of these cells in mucosal immunity, (2) the patterns of gene expression induced by environmental oxidant pollutant exposure that lead to increased susceptibility of asthmatics to virus-induced exacerbation of their disease, (3) the mechanisms through which the oxidant pollutant ozone contributes to morbidity in normals and allergic asthmatics, and (4) the airway epithelial pathways of metabolism and synthesis of active metabolites of environmental agents that induce cytotoxic or carcinogenic effects.

Virginia Weaver, MD, MPH

Virginia Weaver's research interests involve the use of molecular epidemiology tools in the evaluation of populations exposed to occupational and environmental chemicals. One of the goals of Dr. Weaver's research is to improve risk assessment and medical surveillance through the validation of exposure and early biological effect markers. An additional goal is the inclusion of children in population studies in order to provide data on this susceptible group.

She has two main areas of focus. She is studying the use of biomarkers for benzene exposure in urban populations, including children. Previously used exposure markers for this known human carcinogen have been limited by non-specificity. A specific marker would be very helpful in the protection of populations exposed to this common urban air pollutant. Her second main area of research is the renal impact of exposure to occupational and environmental toxicants. Currently, she is studying clinical and early biological effect markers (urinary retinol-binding protein and N-acetyl-beta-D-glucosaminidase [NAG]) for the renal system in lead workers in South Korea. This work has revealed that renal function decline is most evident in workers as they age. Genetic susceptibility for adverse renal outcomes related to toxicants is another area of study in this project.

Dr. Weaver's clinical activities also involve biomarker applications, thus complementing her research. These activities include management of a medical surveillance program for cadmium-exposed workers in which blood and urine cadmium and beta-2 microglobulin are monitored. In addition, she is a co-investigator in a medical surveillance program for former workers at Los Alamos National Laboratory. This project involves workers with many previous exposures and uses the lymphocyte proliferation test to assess for presence of sensitization from previous beryllium exposure.

TinaMarie Lieu

TinaMarie Lieu received her bachelor's degree from UC Berkeley and majored in molecular and cell biology. Currently, her interests are in researching the effects of glial-derived neurotrophic factor (GDNF) and its role on calcium-activated large-conductance K+ (BK) channels in hypoxic chemotransduction of mouse carotid body.

Blake A. Bennett

Blake is a second year PhD student in the division of physiology in the department of Environmental Health Science.  He is studying the effects of particulate matter on the lung and heart. Blake received his Bachelor of Science in Biology from Wichita State University. He spent 2 years as a laboratory technician for the Environmental Protection Agency studying the effects of endocrine disrupters on the reproduction of Xenopus tropicalis.