• B.A. with Honors in Zoology (Cornell University, Ithaca)
• M.D. (Washington University, St. Louis)
• Post-doctoral (Cambridge University, UK)

• With H.A. Schneiderman, D.C. Tosteson, DE Goldman, and A.L. Hodgkin.

• Associate Professor/Professor of Physiology and Biophysics at Washington University, St. Louis (1968-1980)
• Professor and Chairman, Department of Physiology at the University of Maryland School of Medicine, Baltimore (1979-2003)
• Director, Maryland Center for Heart, Hypertension and Kidney Disease (1987-present)
• Professor of Physiology and Medicine, University of Maryland School of Medicine, Baltimore (1979-present)
• Affiliate Professor, Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore (2005-present)

Calcium ions play essential roles in most cellular activities, including fertilization, cell division, motility and contraction, excitability and secretion. Moreover, altered Ca²⁺ regulation and signaling play central roles in many pathological conditions. My research concerns the regulation of the intracellular Ca²⁺ concentration and its role in normal and pathological cell signaling, especially in vascular smooth muscle (with a focus on the pathogenesis of salt-dependent hypertension) and in the nervous system.

The sarcoplasmic/endoplasmic reticulum (S/ER) accumulates and stores Ca²⁺ for subsequent release as "signal Ca^2+". We identified a "signaling complex" region, termed the "PlasmERosome", that regulates Ca²⁺ storage and signaling. The PLasmERosome consists of three main elements: certain plasma membrane (PM) microdomains, the adjacent "junctional" S/ER (jS/ER), and the tiny pocket of cytosol between the PM and jS/ER. Ca²⁺ is regulated within this cytosolic region by specific ion channels, transporter isoforms and receptors contained in the PM microdomains. This, in turn, regulates Ca²⁺ storage and Ca²⁺ release (i.e., the Ca²⁺ signals) from the S/ER. We are identifying the component transporters within these complexes and determining how the complexes are organized and how they influence local and global Ca²⁺ concentrations and signaling. We employ a variety of molecular and cellular biological methods, including digital imaging. Several transgenic mouse lines are used to study cardiovascular parameters in intact animals, and the properties of isolated small arteries, individual myocytes, and cultured myocytes, neurons and astrocytes. Our findings are unraveling the molecular links between salt and hypertension, and details of synaptic function in neurons.

Specific questions currently being addressed include:

The biological preparations we use include: intact rats and mice, isolated small arteries,freshly isolated or cultured arterial smooth muscle cells, primary cultured neurons and glial cells, and neuronal slice cultures. Transgenic animals (e.g., those with knock-out or overexpression of specific Na⁺ and Ca²⁺ transporters) as well as normal animals are used.

The techniques we employ include: application of molecular and cell biological methods (e.g., immunoblotting, immunoprecipitation, PCR, and construction of DNAs, adenoviral vectors and anti-sense probes or silencer RNA, patch clamping, and high-resolution digital (fluorescence) microscopy. The latter is used for immunocytochemical detection of ion transporters, and for ion concentration monitoring with ion-sensitive dyes (including novel Ca²⁺ sensors introduced by transfection). Microscopy methods include standard wide-field and confocal fluorescence, 3-D image reconstruction, and analysis of near-membrane phenomena with lipophilic cation-sensitive indicators, targeted Ca²⁺-sensitive fluorescent proteins and TIRF. Hemodynamics is studied with telemetry in intact, conscious animals and with echocardiography in lightly anesthetized mice.