Ivet Bahar, PhD

Distinguished Professor and JK Vries Chair, Computational & Systems Biology Department

Biomolecular systems dynamics at multiple scales; evolution of proteins' sequence, structure, dynamics and function; computer-aided drug discovery and polypharmacology; network models for protein-protein interactions, supramolecular machinery and allostery; modeling and simulations of membrane proteins dynamics and mechanisms of interactions.

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Jeffrey Brodsky, PhD

Avinoff Professor of Biological Sciences

Research in the Brodsky lab is devoted toward understanding how proteins in the secretory pathway are subject to protein quality control and how molecular chaperones and components of the ubiquitin-proteasome machinery mediate this event. Our work contributed to the discovery of the ER associated degradation (ERAD) pathway, and ongoing studies are geared toward deciphering the mechanisms underlying this pathway using biochemical and genetic attacks in both yeast and mammalian cells.  The importance of ERAD is evidenced by the fact that >70 human diseases are associated with ERAD, and a growing number of distinct ERAD substrates play vital roles in human physiology.  In parallel, we have developed novel classes of small molecule modulators of molecular chaperone function, some of which show efficacy for protein conformational disorders in model systems.

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Edward A. Burton, MD, DPhil, FRCP

Associate Professor of Neurology, Associate Professor of Microbiology and Molecular Genetics, UPMC Endowed Chair in Movement Disorders

Many human movement disorders are caused by protein misfolding and aggregation in neurons and glia.  Parkinson's disease and multiple system atrophy are characterized by accumulation of misfolded alpha-synuclein, whereas misfolded MAP-tau accumulates in progressive supranuclear palsy and corticobasal degeneration.  In addition, primary torsion dystonia is caused by loss of function of torsin, an endoplasmic reticulum chaperone.  We have generated novel zebrafish models allowing us to study the pathogenesis of these diseases and to isolate chemical modifiers as a first step towards drug discovery.  We also have a research program evaluating gene therapy approaches in these diseases.

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Carlos J. Camacho, PhD

Associate Professor, Department of Computational Biology

Dr. Camacho is a computational biophysicist, with expertise in the areas of protein folding, binding, regulation, and drug discovery. He is particularly interested in understanding the role of flexibility and intrinsically disordered protein regions in regulatory functions. Past accomplishments include revealing the role of desolvation in protein specificity; describing the role of anchor residues as key determinant of molecular recognition; and, developing the first automated method to predict docked proteins “ClusPro”. More recently, the Lab of Dr. Camacho has revolutionize rational drug discovery by developing the first interactive technologies for virtual screening, including the development of novel libraries specially designed to disrupt protein-protein interactions. 

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Charleen Chu, MD, PhD

Professor of Pathology, Julio Martinez Chair in Neuropathology

My laboratory studies organelle homeostasis, compartmentalized signals and cellular quality control in genetic and toxin models of neurodegeneration. In particular, we are interested in the mitochondrial lifecycle, and the role of proteins mutated in Parkinson’s disease, dementia and hereditary mitochondrial diseases in regulating neuron morphology and health. Using cell biologic, molecular imaging and mass spectrometry approaches, my team studies post-translational modifications and transcriptional (mtDNA and nDNA) mechanisms that mediate catabolic-anabolic imbalances in neurodegeneration.

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Chris Donnelly, PhD

Assistant Professor, Neurobiology

Our laboratory studies the pathobiology underlying neurodegenerative diseases. We are interested in the discovery of pathways whose dysfunction contributes to neuronal death observed in a motor neuron disease, Amyotrophic Lateral Sclerosis (ALS), and dementias such as Frontotemporal Dementia (FTD). A hallmark neuropathological feature of neurodegenerative diseases is intracellular protein inclusions. We employ novel approaches to assess both the molecular triggers that initiate inclusion formation and identify modifiers of these pathological inclusions. Commonly used strategies in our laboratory include the generation of induced pluripotent stem cell neurons from ALS/FTD patient fibroblasts, optogenetic induction of neurodegenerative proteinopathies, and light-induced assembly of functional membraneless ogranelles.

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Yvonne Eisele

Assistant Professor of Medicine

Cell Biology and Cellular Dysfunction, Disease Causing Mutations, Disease Models and Aggregation, Defective Protein Folding, Neurodegeneration in Model Systems


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Raymond A. Frizzell, PhD

Director, Cystic Fibrosis Research Center, Departments of Pediatrics and Cell Biology

Our group is interested in the mechanisms of salt and water transport across absorptive and secretory epithelial cells.  Our focus is on the biogenesis and quality control pathways that determine ion channel expression, trafficking and the mechanisms that govern channel density at the cell surface.  Our main interest concerns the CFTR anion channel, where myriad mutations produce the genetic disease, cystic fibrosis, via diverse cellular mechanisms.

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J Timothy Greenamyre, MD, PhD

Love Family Professor and Vice-Chair of Neurology, Director, Pittsburgh Institute for Neurodegenerative Diseases, Chief, Movement Disorders

Dr. Greenamyre is interested in defining mechanisms of neurodegeneration in order to identify new targets for development of neuroprotective (‘disease-modifying’) therapeutic strategies. Most of our current work is on Parkinson’s disease (PD), and we are particularly interested in mitochondrial abnormalities and their roles in causing oxidative damage, protein aggregation and neurodegeneration.

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Angela Gronenborn

UPMC Rosalind Franklin Professor and Chair, Distinguished Professor of Structural Biology

Our laboratory combines NMR spectroscopy with Biophysics, Biochemistry, and Chemistry to investigate cellular processes at the molecular and atomic levels in relation to human disease. We presently focus on three main areas in biology: HIV pathogenesis, structural methods, such as NMR spectroscopy and X-ray crystallography, protein-carbohydrate recognition, and protein deposition diseases. In order to understand how biological macromolecules work and intervene in a rational manner with respect to activity and function, detailed knowledge of their architecture and dynamic features is required. Evaluation of the major determinants for stability and conformational specificity of normal and disease-causing forms of these molecules, will allow us to unravel the complex processes associated with disease.

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Neil Hukriede, PhD

Associate Professor, Vice Chair, Department of Developmental Biology

Acute kidney injury (AKI) is associated with high mortality and morbidity and AKI survivors often develop end stage renal disease. At present, there are no established therapies to prevent renal injury or accelerate the rate of renal recovery following AKI.  The Hukriede lab performs chemical screens to identify compounds that enhance kidney regeneration by increasing the rate of renal recovery and decreasing fibrosis. 

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Thomas R. Kleyman, MD

Chief, Renal-Electrolyte Division, Sheldon Adler Professor of Medicine, Professor of Cell Biology

The Kleyman laboratory focuses on studies of Na and K  channels that are found in epithelia. How are epithelial Na channels regulated by extracellular factors, including Na, shear stress, and proteases? What are the roles of epithelial Na channels in non-epithelial tissues? What are the roles on WNK kinases in facilitating adaptive changes in K channel expression in response to increased dietary K intake?

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Todd Lamitina, PhD

Associate Professor of Pediatrics and Cell Biology

Work in the Lamitina Lab utilizes the model organism C. elegans to define mechanisms of age-related neurodegenerative diseases, such as ALS.  The lab also investigates how stress responses are coordinated at the organismal level.  The accumulation of conformationally aberrant proteins is a focus of both research projects.  Through our work, we hope to understand if 'natural' mechanisms for opposing protein misfolding (i.e. stress responses) might be leveraged for the treatment of these currently incurable neurological diseases.

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Rehana Leak, PhD

Associate Professor of Pharmacology, Duquesne University, Adjunct Assistant Professor of Neurology, University of Pittsburgh

The major research foci of the Leak lab include 1) the transmission of proteinopathic stress across neuroanatomical circuitry in Parkinson’s disease and 2) adaptive responses to subtoxic proteinopathic and oxidative stress—a phenomenon known as preconditioning or tolerance. Recent studies in Dr. Leak’s lab have established that α-synucleinopathy can be transmitted from superficial olfactory structures deep into the brain in vivo, consistent with the olfactory vector hypothesis of Parkinson’s disease, and have provided evidence for robust cross-hemispheric preconditioning of the nigrostriatal pathway in an animal model of Parkinson’s disease.

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Allyson F. O’Donnell, PhD

Assistant Professor, Department of Biological Sciences, Duquesne University

Research in the O’Donnell lab focuses on the molecular mechanism underlying selective protein trafficking. Specifically, we use studies of alpha-arrestins, a recently identified class of trafficking adaptor, to define key events in molecular selection and post-translational regulation of protein trafficking, as well as to define previously uncharacterized protein trafficking pathways. Our work uses the budding yeast Saccharomyces cerevisiae as a model system and we are currently applying insights from yeast to guide directed studies in mammalian cells. 

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Udai Pandey

Associate Professor Department of Pediatrics, Human Genetics & Neurology Children's Hospital of Pittsburgh

Neurodegeneration in Model Systems, Disease Models & Protein Aggregation, Disease Causing Mutations

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Alexander Sorkin, PhD

Professor and Chair, Department of Cell Biology

Research in the Sorkin laboratory is currently split into two major directions which are apparently distinct from each other with respect to the cell type, relation to the human disease, and experimental models used. However, the main idea underlying both directions is conceptually the same - to understand how trafficking regulates function(s) of transmembrane proteins, such as receptors and transporters. One major project aims at elucidating the molecular mechanisms of endocytosis of growth factor receptors and analyzing the role of endocytosis in regulation of signal transduction by these receptors using a prototypic member of the family, epidermal growth factor (EGF) receptor as the main experimental system. Another major research direction is the study of the role of trafficking processes in the regulation of the plasma membrane dopamine transporter in central nervous system. In both of these research areas we are using a multidisciplinary approach, and a combination of in vitro and in vivo experimental models.

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Arohan R. Subramanya, MD, FASN

Assistant Professor of Medicine and of Cell Biology, Staff Physician, Research and Medicine Services

Dr. Subramanya is studying the molecular physiology and cell biology of SLC12 co-transporters, transport proteins that control blood pressure, cell volume, and electrolyte balance. This family of transport proteins includes the thiazide-sensitive Na-Cl co-transporter NCC, and the bumetanide-sensitive Na-K-2Cl cotransporter NKCC2, kidney salt transporters that are targets for diuretic therapies commonly prescribed in the clinic.  His laboratory has defined molecular networks that control the activity, folding, and biosynthetic processing of these co-transporters. These studies have revealed new insights into the molecular basis of human hypertension and hereditary salt wasting kidney diseases, such as Gitelman and Bartter syndromes.

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Amantha Thathiah, PhD

Assistant Professor, Department of Neurobiology

The focus of the research in the Thathiah lab is to study the cellular and molecular mechanisms involved in the pathogenesis of Alzheimer´s disease (AD). Neuropathologically, the brains of AD patients are characterized by the accumulation of aggregates of the amyloid-β (Aβ) peptide and neurofibrillary tangles, which are composed of the hyperphosphorylated microtubule-associated protein tau. The Thathiah lab investigates the involvement of G protein-coupled receptors (GPCRs) in modulation Aβ and tau pathology and the cross-talk between Aβ and tau in disease progression. We combine cellular and biochemical techniques with mouse models of neurodegeneration and behavioral studies to address our research questions.

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Patrick Thibodeau, PhD

Assistant Professor, Department of Microbiology and Molecular Genetics

My research is focused on understanding how protein folding underlies human disease with a focus on ATP-Binding Cassette (ABC-) proteins.  Studies in my laboratory explore the relationships between primary amino acid sequence and the acquisition of native protein structure and function and are focussed on cystic fibrosis (CFTR) and pseudoxanthoma elasticum (ABCC6).  We utilize a combination of structural, biophysical and cell biological approaches to elucidate the folding pathways of the wildtype proteins and their alteration by mutation.     

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Ron Wetzel, PhD

Professor, Department of Structural Biology

We study the mechanisms of misfolding and misassembly of medically relevant peptides into multimers, various kinds of oligomers and amyloid fibrils, and in several ways are probing the relevance of these assembly states to neurodegeneration in Huntington's disease and Alzheimer's disease.  We are developing mutated forms of these peptides that alter aggregation pathways in cis and in trans that can be used to probe the toxicity of various assembled states in cell and animal models.  We have also been using advanced fluorescence techniques and other methods to directly determine the growth time dependent levels of various assembly states in dysfunctional and dying cells.

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Peter Wipf, PhD, Dipl. Chem., FRSC, AAASF, ACSF

Distinguished University Professor of Chemistry, Professor of Pharmaceutical Sciences and Bioengineering, Co-Leader, UPCI CTP

Our research interests include the total synthesis of natural products, organometallic, heterocyclic, medicinal and computational chemistry. We study chemical reactivity, develop synthetic methods to augment the chemical toolbox, and collaborate to develop new therapeutics.

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