Biochemistry and Molecular Biophysics Graduate Group

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pixelBiomedical Imaging and Supramolecular Assemblies

Ben E. Black, Ph.D.

Chromosome segregation; chromatin structure; epigenetic centromere specification; hydrogen/deuterium exchange

Associate Professor of Biochemistry & Biophysics
913A Stellar-Chance Labs
Tel: 215-898-5039 (office) / Fax: 215-573-7058
Lab: 912 Stellar Chance Labs
Tel: 215-898-4476 (lab)
Departmental website

Dr. Black's laboratory is interested in how particular proteins direct accurate chromosome segregation at mitosis. In humans, the chromosomal element—the centromere—that directs this process is not defined by a particular DNA sequence. Rather, the location of the centromere is dictated by an epigenetic mark generated by one or more resident proteins. These centromeric proteins interact directly with the DNA to create a specialized chromatin compartment that is distinct from any other part of the chromosome. By taking biophysical, biochemical, and cell biological approaches, our work is to define the composition and physical characteristics of the protein and protein/DNA complexes that epigenetically mark the location of the centromere on the chromosome. This work involves building centromeric chromatin from its component parts for analysis of its physical characteristics, developing biochemical assays to reconstitute steps in the process of establishing and maintaining the epigenetic mark, and using cell-based approaches to study the behavior of proteins involved in centromere inheritance and other essential aspects related to chromosome segregation at cell division.


Theresa M. Busch, Ph.D.

Photodynamic therapy, tumor microenvironment

Research Associate Professor of Radiation Oncology
8-126 Smilow Center for Translational Research
Tel: 215-573-3168 / Fax:215-898-0090
Departmental website

Our primary research focus is the investigation of photodynamic therapy (PDT) for the treatment of solid malignancies. In PDT, diseased tissue is illuminated by specific wavelengths of visible light after the delivery of a photosensitizer to that tissue. The light-excited photosensitizer interacts with oxygen to produce reactive oxygen species that damage the tissue and its associated stroma, including the supporting vascular network.

Our research centers on the study of biophysical limitations of treatment response to PDT. This includes the study of heterogeneities in the distributions of oxygen, photosensitizing drug, and light. Our studies have found that PDT can create widespread, severe hypoxia during illumination, even in tumor cells immediately adjacent to perfused blood vessels. Furthermore, noninvasive monitoring has shown PDT effect on tumor oxygenation and blood flow during the illumination period to be predictive of an animal’s long-term response to therapy. Such findings are extremely relevant to clinical PDT applications, where significant heterogeneity in hypoxia and photosensitizer distributions among the tumors of PDT patients will contribute to variable therapeutic outcomes. Indeed, we have documented a relationship between biochemical (PSA) response to PDT in prostate cancer patients and levels of photosensitizer drug and light energy in their prostates. Ultimately, in order to improve the clinical therapeutic index and efficacy of PDT, we aim to alter the microenvironment of tumors undergoing treatment as guided by noninvasive monitoring of their response.


Roger Greenberg, M.D., Ph.D.

Basic DNA repair mechanisms that impact cancer etiology and therapy

Associate Professor of Cancer Biology
513 Biomedical Research Building II/III
Office: (215) 746-2738 / Lab: 215-746-7799/ Fax: (215) 573-2486
Lab website

My laboratory uses a multifaceted experimental approach to investigate basic mechanisms of DNA repair that impact cancer etiology and response to therapy. We have a particular interest in understanding chromatin dependent contributions to DNA repair and their impact on the function of breast and ovarian cancer suppressor proteins BRCA1 and BRCA2. In relation to these interests, we have developed novel methodologies to visualize DNA double-strand break responses in real time at the single cell level (Shanbhag et al. Cell 2010; Cho et al. Cell 2014) and used these approaches to define basic features of DNA double-strand break recognition, communication between DNA damage responses and transcription on contiguous stretches of chromatin, and implicate homologous recombination as a key driver of chromatin mobility and alterations to higher order structure.

We provided the first insights into the molecular nature of BRCA1 double-strand break recognition events by reporting that BRCA1 is targeted to lysine63-linked ubiquitin chains at damaged chromatin (Sobhian et al. Science 2007). This occurs through BRCA1 interaction with a 5-membered ubiquitin binding protein complex that selectively interacts with lysine63-linked (K63-Ub) ubiquitin chains. This work implicated nondegradative ubiquitin chains as a recognition signal for the assembly of DNA repair protein complexes at damaged chromatin. Our subsequent studies provided insights into the importance of ubiquitin signaling to BRCA1 dependent DNA repair and tumor suppression (Jiang et al. Genes & Dev 2015; Solyom et al. Science Transl Med 2012; Sawyer et al. Cancer Discov 2015). A second and emerging area of interest in my laboratory is the relationship between homologous recombination and alternative telomere maintenance mechanisms (ALT). We have recently reported a specialized homology searching mechanism is responsible for ALT telomere recombination and developed the tools to visualize this process in real time (Cho et al. Cell 2014). My laboratory will continue this research to define alternative mechanisms of homologous recombination and their functional relationship to telomere maintenance in ALT dependent cancers. Finally, we have devoted considerable effort to understanding the biochemical, structural, and in vivo functions of Zn2+ dependent (JAMM Domain) deubiquitinating enzymes, which play vital roles in the DNA damage response and in inflammatory cytokine signaling.  We have active collaborations that have revealed the structural basis for JAMM domain DUB activation (Zeqiraj et al. Mol Cell 2015) and have developed first in class inhibitors of such enzymes for disease indications that emanate from elevated interferon responses.


Michael A. Lampson, Ph.D.

Chromosome segregation in mitosis and meiosis, biosensors for mitotic kinases

Associate Professor of Biology
204-I Carolyn Lynch Laboratory
433 South University Ave.
Philadelphia, PA 19104
Tel: 215-746-3040
Lab website

Within the broad theme of cell division, our research is currently focused in two areas:
1. Mechanics of cell division, particularly interactions between chromosomes and spindle microtubules and regulation by mitotic kinases.
2. Cell biological principles driving chromosome evolution through biased (i.e., non-Mendelian) chromosome segregation in meiosis.


Zhe Lu, M.D., Ph.D.

Structure-function relationship of ion channels; molecular mechanisms of protein-protein interactions

Professor of Physiology
728 Clinical Research Building
Tel: 215-573-7711 / Fax: 215-573-1940
Departmental website

Dr. Lu's laboratory investigates the molecular and the biophysical mechanisms of inward-rectifier potassium channels and cyclic-nucleotide-gated channels, using a combined approach of biophysics, biochemistry and molecular biology. Specifically, they investigate the channel mechanisms that enable the inward-rectifier potassium channels to control cardiac pacemaker rate, to regulate communication strength between neurons and to couple blood glucose level to insulin secretion, and the mechanisms that enable the cGMP-gated channel to mediate visual photo-transduction in the eye. Additionally, they develop specific inhibitors for various types of physiological and pathophysiological important ion channels through both passive screening and active design.


E. Michael Ostap, Ph.D.

Biochemistry of contractile proteins, biophysics of cell motility, and characterization of unconventional myosins

Professor of Physiology
Director, Pennsylvania Muscle Institute
700A Clinical Research Building
Tel: 215-573-9758 (office); 215-898-3685 (lab) / Fax: 215-573-1171
Lab website

The goal of our research is to understand the function, regulation, and molecular mechanism of the ubiquitously expressed molecular motors called myosins. The physiological roles and molecular mechanisms of many members of the myosin superfamily are not well understood. To better define the roles of myosin isoforms, we are using a rigorous interdisciplinary approach that combines chemistry, biophysics, cell, and molecular biology. We are obtaining a physical framework in which to discuss the cellular functions of myosins by investigating the enzymatic and structural properties of native and recombinant myosin isoforms, and we are investigating the in vivo localization, organization, dynamics, and physiology of myosin-I in fixed and live cells using high-resolution microscopy techniques.


Amish Patel, Ph.D.

Predictive computational framework for characterizing biomolecular hydration, interactions and assemblies

Reliance Industries Term Assistant Professor
Department of Chemical and Biomolecular Engineering
311A Towne Building
Tel: 215-898-9682
Lab website

The last two decades have seen an incredible revolution in structural biology: over 90,000 protein structures have now been solved at atomic resolution. Translating this wealth of static structural information into a molecular understanding of dynamic intracellular processes represents a grand challenge in molecular biology, with grave implications on our understanding of human health and disease. Progress in this area hinges on our ability to understand, predict, and manipulate the interactions of various proteins, given their precise structure, i.e., out of the veritable menagerie of molecules that a protein encounters in the cellular milieu -- ligands, peptide fragments, nucleic acids, membranes, and other proteins -- which molecules will it interact favorably with, how strong will the interaction be, and what are the strategies for modulating the interaction strength?

Based on recent work in our group and those of others, we hypothesize that the biggest challenge in accurately predicting protein interactions is precisely accounting for the role of water in mediating these interactions. Because all of biology happens in water, every biomolecular binding process requires the dehydration of the binding partners, with direct interactions between them replacing their individual interactions with water. While the direct interactions are straightforward to estimate, the protein-water interactions are difficult to quantify because proteins have incredibly complex surfaces that disrupt the inherent structure of water (strong hydrogen bonds) in countless different ways. So, what makes predicting protein interactions particularly challenging, is quantifying this disruption of the hydration shell water structure, which depends not only on the chemistry of the underlying protein surface, but also on the precise topography and chemical pattern of amino acids. Using principles of liquid state theory in conjunction with novel simulation techniques, we are working towards developing a framework, which will transform our ability to accurately and efficiently predict protein interactions, and provide a basis for understanding how proteins respond to various perturbations, aggregate into multi-meric assemblies, and are able to function.


Ravinder Reddy, Ph.D.

Sodium and oxygen-17 MR methods; multiple quantum and polarization transfer MR techniques

Professor of Radiology
Director, Center for Magnetic Resonance and Optical Imaging
B1-Stellar-Chance Labs
Tel: 215-898-5708 / Fax: 215-573-2113
MMRRCC website / Lab website

My research interests are in developing novel, multinuclear (²³Na, ¹?O, ¹³C and ¹H) magnetic resonance imaging and spectroscopic techniques for early diagnosis and quantification of physiological and functional parameters in pathologies such as arthritis, stroke, cancer and Alzheimer’s Disease. Our pulse sequence developmental approaches exploit quadrupolar spin-dynamics, polarization transfer, multiple quantum coherences, indirect detection and spin locking for studying molecular dynamics in biological tissues in vivo. In particular, sodium and spin-locking MRI are targeting to map proteoglycan molecules (e.g. Aggrecan) in the connective tissues in vivo. Indirect ¹?O MRI is aimed at studying cerebral blood flow and cerebral oxidative metabolism and tumor perfusion and metabolism. Spin-locking MRI is being developed to impart novel contrast in various tissue types (brain, connective tissues and tumors), macromolecular ordering in tissues, and visualize and quantify Amyloidal plaques in Alzheimer’s disease in vivo


Elizabeth Rhoades, Ph.D.

Functional and dysfunctional mechanisms of intrinsically disordered proteins


Associate Professor of Chemistry
258 Chemistry Building
Tel: 215-573-6477 / Fax: 215-573-2112

Research in the Rhoades lab aims to elucidate the principles that link protein conformational change with structure-function relationships, focusing on understanding structural plasticity in intrinsically disordered proteins (IDPs). IDPs do not form stable structures under physiological conditions; for many, function is dependent upon disorder. This is in striking contrast to the structure-function paradigm that dominates our understanding of globular proteins. Given the large fraction of the eukaryotic proteome predicted to be disordered, the scope of the problem and the need for new insights are enormous.

Much of our effort is directed towards IDPs whose aggregation is central to the pathology of several degenerative diseases: α-synuclein (Parkinson’s disease), tau (Alzheimer’s disease), and IAPP (Type II Diabetes). These three proteins have diverse native functions and binding partners, but share intriguing commonalities of toxic mechanism and the importance of templated selfassembly. Studying systems in parallel allows us to generate protein and disease-specific insights as well as determine principles relevant to general functional and dysfunctional mechanisms of IDPs. Our primary approaches center on single molecule optical techniques. These approaches enable quantitative and structural assessments of our systems in isolation and in the context of biologically relevant interactions. Single molecule approaches are unique in their ability to characterize systems which exist and function as a dynamic ensemble of states.


Phong Tran, Ph.D.

Cytoskeleton organization and cellular pattern formation

Associate Professor of Cell & Developmental Biology
1009 Biomedical Research Building II/III
Tel: 215-746-2755 / Fax: 215-898-9871
Departmental website

The Tran lab is interested in understanding how positional information is generated within the cell by the cytoskeleton. For example, their previous studies in fission yeast have shown that bundles of microtubules can set up a spatial map for the cell to know where to grow and where to position its nucleus. Microtubule architecture and dynamics are influenced by both plus- and minus-end microtubule-associated-proteins. A long-term goal, then, is to understand what role these proteins play in the establishment and maintenance of cellular spatial domains by microtubules. The Tran lab plans to: 1) identify the molecular components of the microtubule organizing centers, 2) define the interactions of known microtubule-associated-proteins with the microtubule ends and the roles of these proteins in bringing about proper nuclear positioning and cellular pattern, and 3) develop and apply advanced optical imaging and analysis methods to the yeast system


Andrew Tsourkas Ph.D.

Molecular imaging, drug delivery, nanotechnology, and biotherapeutics

Professor of Bioengineering
110 Hayden Hall
Tel: 215-898-8167
Lab website

The overall goal of my research program is to develop novel molecular imaging agents and targeted therapeutics. We envision that these agents will provide basic scientists with unique insight into disease mechanisms and clinicians with the necessary information to make earlier and more accurate diagnoses and treatments that are tailored for individual patients. Our efforts are primarily focused on (i) nanocarrier synthesis, characterization, and site-specific bioconjugate chemistry for targeted imaging and therapeutic applications and (ii) the imaging of RNA in living cells. My lab has experience preparing a wide range of nanoparticle formulations (e.g. gold, iron oxide, liposomes, polymersomes, micelles, etc.). Recently, we also developed several new bioconjugation techniques that allow for the site-specific and efficient functionalization of targeting ligands with various cargo (e.g. nanoparticles, imaging agents, drugs, etc.) In addition to working in the fields of nanomedicine and targeted therapy, we are also interested in developing new tools to image RNA in living cells. Recently, we developed a new oligonucleotide-based probe, ratiometric bimolecular beacon (RBMB), that can be used to acquire a quantitative measure of RNA expression at the single cell level by both fluorescence microscopy and flow cytometry.


Sergei A. Vinogradov, Ph.D.

Functional macromolecules, optical imaging probes, porphyrin chemistry, dendrimer chemistry, oxygen microscopy and tomography

Associate Professor of Biochemistry & Biophysics
1013B Stellar-Chance Labs
Tel: 215-573-7524
Departmental website

Dr. Vinogradov's research revolves around functional molecular systems related to biological objects by function or application. We use methods of synthetic organic chemistry to design and construct molecules with predefined degree of active site encapsulation, photophysical properties and tunable energy and electron transfer pathways. Our special area of interest is construction of advanced probes for optical microscopy and imaging. We are developing methods for imaging of oxygen in biological tissues using phosphorescence quenching, including near infrared tomography by phosphorescence lifetime and two-photon microscopy of oxygen. These techniques are expected to provide useful tools for research in cancer, diabetes, ophthalmology and neuroscience. Two areas of chemistry are recurrent in our research: porphyrins and dendrimers. We study photophysics, acid/base properties and electrochemistry of aromatically pi-extended porphyrins, addressing various structure-property relationships in this porphyrin family.


Felix W. Wehrli, Ph.D.

MRI of biomaterials microstructure, mathematical modeling, image processing

Professor of Radiology, and Biochemistry & Biophysics
1 Founders Pavilion
Tel: 215-662-7951 / Fax: 215-662-7263
LSNI website

Research of the Laboratory is aimed at quantitatively characterizing tissue microarchitecture and its relationship to physiology and function by means of spatially resolved nuclear magnetic resonance in animals and humans. The current focus of the Laboratory is on the development of new methods for the quantitative assessment of metabolic bone disease by means of the MR-based "virtual bone biopsy", and new methods for the study of bone matrix and mineral micro- and nanostructure. A second line of research focuses the development of MRI-based methods for noninvasive measurement of blood oxygen saturation Additional projects deal with ultrahigh-resolution microscopy of neuronal architecture in spinal cord injury models as well as methods for indirect assessment of tissue microstructure by means of diffusion diffraction and multiple quantum coherence imaging.


John W. Weisel, Ph.D.

Structural studies of molecular/cellular mechanisms in blood clotting and fibrinolysis

Professor of Cell & Developmental Biology
1154 Biomedical Research Building II/III
Tel.: 215-898-3573 / Fax: 215-898-9871
Lab website

The research in this lab has focused on the molecular and cellular mechanisms of blood coagulation and fibrinolysis, as analyzed through the use of various biophysical and structural techniques, including visualization of molecules and supramolecular aggregates and measurements of mechanical properties of cellular and extracellular structures. Molecular mechanisms of the dissolution of the clot by the fibrinolytic system are under investigation. The interactions of integrins with various adhesive proteins and with the cytoskeleton is also a focus of research. The results of these studies have implications for basic mechanisms of protein-protein and protein-cell interactions as well as for clinical aspects of hemostasis, thrombosis and atherosclerosis.




Walter R.T. Witschey

Structural studies of molecular/cellular mechanisms in blood clotting and fibrinolysis

Assistant Professor of Radiology
7-103 Smilow Center for Translational Research
Tel.: 215-662-2310 (office) /215-746-4048 (lab)
Lab website

The Witschey lab studies cardiovascular disease using non-invasive imaging and computational biology approaches. Our primary goal is the creation of new therapies and risk prediction strategies for ischemic heart disease and arrhythmias. Some examples of our recent work include quantitative mapping of myocardial scar and salvage with magnetic resonance imaging and optical imaging. A recent focus of our lab is image-guided systems for cardiovascular surgery, myocardial repair and treatment of arrhythmias. We use a bench-to-bedside approach, developing multiscale approaches from in silico designs and animal models to clinical Radiology and Cardiology.

            We have a particular interest in dynamic and real-time imaging of cardiovascular function, myocardial work and energetics in patients with heart disease. We are applying these methods to non-invasively measure regional myocardial material properties, understand hemodynamics after surgical therapy and study the relationship between myocardial conduction and imaging biomarkers of fibrosis in the context of RF ablation therapy. To achieve this goal, our focus is superfast sampling and reconstruction of MRI data, multiradiofrequency detectors and unconventional signal detection.