USA Department of Biochemistry & Molecular Biology Faculty

Academic Faculty

▼   Ronald D. Balczon, Ph.D.

Ronald D. Balczon, Ph.D.Ronald D. Balczon, Ph.D.

Associate Professor

Postdoctoral Studies, Baylor College of Medicine and University of Alabama at Birmingham
Ph.D., Florida State University

Recent Publications

Research Interests

My research is focused on the role of the microtubule cytoskeleton in health and disease.  Our past research has investigated how microtubules maintain the pulmonary endothelial cell barrier and how disruption of microtubules leads to pulmonary edema.  These studies have identified a critical role for the microtubule-associated protein tau in maintaining endothelial barrier function and have demonstrated that inhibition of tau activity leads to barrier breakdown and edema.  Our more recent studies have focused on barrier disruption following infection with Pseudomonas aeruginosaPseudomonas aeruginosa infection is a principal cause of acute pneumonia that can progress to sepsis, acute lung injury, and death.  During infection, Pseudomonas uses a type III secretion system to transfer bacterial exoenzymes into the cytoplasm of target cells.  Our studies have shown that one of these exoenzymes, ExoY, targets tau resulting in defective microtubule dynamics, pulmonary endothelial breakdown, and edema.  Studies in progress are investigating long-term effects of Pseudomonas infection on patient health and survival.

Publications 

  1. Wu, S., Chen, H., Alexeyev, M.F., King, J.A.C., Moore, T.M., Stevens, T, and Balczon, R.D. 2007. Microtubule motors regulate ISOC activation necessary to increase endothelial cell permeability. J. Biol. Chem. 282:34801-34808.
  2. Prasain, N., Alexeyev, M., Balczon, R., and Stevens, T. 2009. Soluble adenylyl cyclase-dependent microtubule disassembly reveals a novel mechanism of endothelial cell retraction. Am. J. Physiol. Lung Cell Molec. Physiol. 297:L73-83. PMCID: PMC2711814.
  3. Ochoa, C.D., Stevens, T., and Balczon, R. 2011. Cold exposure reveals two populations of microtubules in pulmonary endothelia. Am. J. Physiol. Lung Cell Molec. Physiol. 300:L132-138.
  4. Sayner, S.L., Balczon, R., Frank, D.W., Cooper, D.M., and Stevens, T. 2011. Filamin A is a phosphorylation target of membrane but not cytosolic adenylyl cyclase activity. Am. J. Physiol. Lung Cell Molec. Physiol. 300:L132-138.
  5. Zeng, H., Pappas, C., Belser, J.A., Houser, K.V., Zhong, W., Wadford, D.A., Stevens, T., Balczon, R., Katz, J.M., and Tumpey, T.M. 2012. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J. Virology 86:667-678.
  6. Ochoa, C.D., Alexeyev, M., Pastukh, V., Balczon, R., and Stevens, T. 2012. Pseudomonas aeruginosa exotoxin Y is a promiscuous cyclase that increases endothelial cell tau phosphorylation and permeability. J. Biol. Chem. 287:25407-25418.
  7. Balczon, R., Prasain, N., Ochoa, C., Prater, J., Zhu, B., Alexeyev, M., Sayner, S., Frank, D.W., and Stevens, T. 2013. Pseudomonas aeruginosa exotoxin Y-mediated tau hyperphosphorylation impairs microtubule assembly in pulmonary microvascular endothelial cells. PLoS One 8:e74343.
  8. Stevens, Tr., Ochoa, C., Morrow, K., Robson, M., Prasain, N., Zhou, C., Alvarez, D., Frank, D., Balczon, R., and Stevens, T. 2014. The Pseudomonas aeruginosa exotoxin Y impairs endothelial cell proliferation and vascular repair following lung injury. Am. J. Physiol. Lung Cell Molec. Physiol. 306:L915-L924.
▼   Donna L. Cioffi, Ph.D.

Donna L. Cioffi, Ph.D.Donna L. Cioffi, Ph.D.

Associate Professor

Ph.D., University of South Alabama, 2006

Recent Publications

Research Interests

Calcium signaling and autoantibodies in pulmonary endothelial barrier disruption.

Our group is interested in endothelial dysfunction in the cardiovascular system. We currently have two major focus areas. The first area is in calcium signaling in pulmonary artery and microvascular endothelial cells as it relates to the formation of inter-endothelial cell gaps and disruption of the endothelial barrier in inflammatory processes. Inflammatory mediators promote endothelial barrier disruption by allowing calcium entry across the plasma membrane through store-operated calcium (SOC) entry channels. Within this focus area we are studying regulation of SOC entry channel activation and inactivation. In one project, we are studying how binding of members of the FKBP family of immunophilins regulates SOC entry activation. In this project we will determine whether glucocorticoid upregulation of FKBP51 inhibits activation of SOC entry which may represent a novel anti-inflammatory mechanism of glucocorticoids.

Another project in the calcium signaling focus area studies the mechanism(s) underlying inactivation of one particular SOC entry channel, the ISOC channel. While it is known that ISOC inactivation is both calcium and phosphorylation dependent, it is not known whether the phosphorylation and calcium mediated pathways are part of a common mechanism. In this project, we are seeking to address the hypothesis that endothelial ISOC inactivation is dependent upon phosphorylation and calcium complexation in the proline-rich region of the ISOC channel subunit TRPC4, and is a critical determinant of the magnitude and duration of inter-endothelial cell gap formation.

The second focus area in our group is that of autoantibodies and endothelial cell dysfunction. It is known that people with some underlying autoimmune diseases are predisposed to developing pulmonary hypertension. Endothelial dysfunction, described as "disordered proliferation and angiogenesis", may play a prominent role in the development and progression of severe pulmonary hypertension. We are interested in determining whether autoantibodies contribute to endothelial dysfunction leading to the development of pulmonary hypertension.

▼   Richard E. Honkanen, Ph.D.

Richard E. Honkanen, Ph.D.Richard E. Honkanen, Ph.D.

Professor and Chair

Ph.D., University of Georgia, 1986

Recent Publications

Research Interests

Protein Phosphatases ( Molecular mechanisms of carcinogenesis; Mechanisms of cardioprotective agents in ischemic myocytes).

The reversible phosphorylation of many proteins determines their biological activity and is a key mechanism controlling intracellular events as diverse as metabolism, contractility, cell division, hormonal action and signal transduction. This phosphorylation/dephosphorylation of proteins occurs on specific serine, threonine, or tyrosine residues and represents a dynamic equilibrium between the activities of both protein kinases and protein phosphatases.

In my laboratory, we are currently studying the molecular mechanisms associated with cancer, coronary heart disease and diabetes. The common theme of our research is the functions of specific protein phosphatases. A major goal of our cancer research is to identify and clone novel protein phosphatases that may play a role in the aberrant proliferative behavior of neoplastic cells. We have also identified a number of natural marine toxins with specific and potent inhibitory activity against certain protein phosphatases. Some of these "toxins" alter the cell cycle progression of tumor cells in culture, and we are interested in determining if these compounds have the potential for development into novel drugs for the treatment of certain cancers. We are also developing techniques to better use these phosphatase inhibitors for the identification of novel protein phosphatases and to study the roles of specific phosphatases in normal and aberrant cellular functions. We are also interested in the identification and development of novel type specific inhibitors.

2011 NIH Director's Transformative RO1 Award: Methods To Enable Cholesterol Catabolism In Human Monocyte Derived Macrophages 

▼   Lawrence L. LeClaire, III, Ph.D.

Lawrence L. LeClaire, III, Ph.D.Lawrence L. LeClaire, III, Ph.D.

Assistant Professor

Ph.D., Florida State University, 2002

Recent Publications

Research Interests

Actin cytoskeleton remodeling and the ARP 2/3 complex in cancer cell metastasis

The crawling motion displayed by amoeboid cells is found in single and multicellular organisms. The molecular mechanism that drives this motion is conserved, but the range of fundamental processes it drives in biology is diverse. For example, single cell soil amoebae crawl through detritus following the chemical cues emitted from microbes prior to engulfing them. Macrophages of the human immune system crawl through tissue in pursuit of pathogens to prevent infection. Both of these cells crawl by protruding lamellipodia from the cell body in a similar fashion. This movement requires the actin cytoskeleton, the cellular engine that provides the forces for amoeboid motility. It is the actin cytoskeleton that drives metastasis and invasion of cancer cells, healing of wounded epithelia, migration of smooth muscle cells in atherosclerosis, and motility of bacterium in host cells. How cells use the same set of cytoskeletal components to build different structures with very different functions and architectures is poorly understood and is the overall focus of my laboratory.

▼   Steve (Ssang-Taek) Lim, Ph.D.

Steve (Ssang-Taek) Lim, Ph.D.Steve (Ssang-Taek) Lim, Ph.D.

Associate Professor

Postdoctoral Studies, University of California, San Diego
Ph.D., University of Alabama at Birmingham, 2003

Visit the Lim Lab Website

Recent Publications

Research Interests

Integrin signaling underlies a multitude of biological phenomenon throughout development, physiological homeostasis, chronic disease progression, and cancer malignancy. We are interested in integrin-associated focal adhesion kinase (FAK) signaling in disease models such as vascular inflammation and cancer metastasis. FAK is a protein tyrosine kinase named for its localization to integrin adhesion sites called focal adhesions. FAK is a converging point of cellular signaling via integrins and growth factor receptors. Interestingly, FAK also localizes to the nucleus to regulate gene expression by controlling a number of transcription factors (e.g., p53, GATA4).

Our current research focus is to understand a molecular mechanism how and why FAK shuttles to convey extracellular/adhesion signals to the nucleus. Based on the recent finding that the nuclear-localized FAK limits GATA4 required for vascular cell adhesion molecule-1 (VCAM-1) transcription and VCAM-1 plays a key role in promoting vascular inflammation by facilitating leukocyte recruitment, we are investigating whether nuclear FAK regulates vascular inflammation. We have genetic FAK mouse models to evaluate an inflammatory role of FAK in vascular injury models.

Another area of our research is to explore a mechanism of tumor metastasis via tumor-stroma interaction. Although the typical metastasis of melanoma to the lymph nodes is detrimental to overall survival of melanoma patients, molecular mechanisms of this process remain elusive. We are investigating the role of FAK-mediated VCAM-1 expression on lymphatic vessel endothelium in melanoma metastasis to the lymph nodes, using a genetic mouse model and FAK inhibitors. Successful completion of the project will reveal a highly significant value of FAK inhibitors as a novel drug for prevention of melanoma metastasis.

Research training positions are available for postdoc and graduate students.

Research training in our lab will provide you skills necessary for studying molecular/cell biology, biochemistry, mouse genetics and also provide you key concepts in cellular signaling, gene expression, cancer biology and vascular biology.

▼   Wito Richter, Ph.D.

Wito Richter, Ph.D.Wito Richter, Ph.D.

Assistant Professor

Ph.D., Leipzig University, Leipzig, Germany, 2000

Recent Publications

Research Interests

Cyclic nucleotide signaling and cAMP phosphodiesterases

Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that regulates a myriad of physiological processes. Its cellular concentration is determined by the rate of its synthesis by adenylyl cyclases and the rate of its degradation by cyclic nucleotide phosphodiesterases (PDEs). The mammalian PDEs encompass a large number of isoenzymes grouped into eleven families. Our laboratory explores the structure, regulation and physiological functions of Type 4 PDEs (PDE4s), the largest and most widely expressed PDE family.

The PDE4 family comprises four genes, PDE4A-D, that together are expressed as more than 25 protein variants. PDE4 inactivation produces a number of therapeutic benefits, including anti-inflammatory and memory- and cognition-enhancing effects, and has been pursued as a therapeutic approach for a number of indications. However, the non-selective PDE4 inhibitors available to date also produce significant side effects that limit their clinical utility. Individual PDE4 variants exert unique and non-overlapping physiological and pathophysiological roles by controlling cAMP levels in microdomains of signaling, to which they are tethered via variant-specific protein/protein or protein/lipid interactions, rather than on the global cellular scale. Our group aims to dissect the roles of individual PDE4 variants in diverse cells and tissues to verify individual PDE4s and PDE4 signaling complexes as drug targets. In addition, we explore regulatory and structural differences between individual PDE4s for the development of isoform-selective PDE4 inhibitors with an improved safety profile compared to the non-selective PDE4 inhibitors available to date.

Research training positions are available for postdoc and graduate students. Email richter@southalabama.edu.

 

Adjunct Faculty

Ahn, Erin Eun-Young, Ph.D.,  Associate Professor 
Mitchell Cancer Institute
Email: eahn@health.southalabama.edu • (251) 445-9805

Singh, Ajay, Ph.D., Professor
Mitchell Cancer Institute
Email: asingh@health.southalabama.edu • (251) 445-9873 

Singh, Seema, Ph.D., Associate Professor
Mitchell Cancer Institute
Email: seemasingh@health.southalabama.edu • (251) 445-9873