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)
Email: blackbe@mail.med.upenn.edu
Black Department 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
Email: buschtm@mail.med.upenn.edu
Busch department 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.

 

Michael A. Lampson, Ph.D.

Chromosome segregation in mitosis and meiosis, biosensors for mitotic kinases

Assistant Professor of Biology
204-I Carolyn Lynch Laboratory
433 South University Ave.
Philadelphia, PA 19104
Tel: 215-746-3040
Email: lampson@sas.upenn.edu
Lampson 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
Email: zhelu@mail.med.upenn.edu
Lu Physiology 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
Email: ostap@mail.med.upenn.edu
Ostap Laboratory Page

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.

 

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
Email: krr@mail.med.upenn.edu
MMRRCC Homepage / Reddy 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

 

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
Email: tranp@mail.med.upenn.edu
Tran Cell and Developmental Biology Homepage

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

Associate Professor of Bioengineering
110 Hayden Hall
Tel: 215-898-8167
Email: atsourk@seas.upenn.edu
Tsourkas lab website

The rapid advancement in our understanding of the regulatory and signaling pathways responsible for cell growth, differentiation, and death has led to the identification of an array of anomalies in the genome and proteome that can be associated with disease. Our laboratory is interested in developing molecular imaging probes that target these anomalies to locate and study diseased states in vivo. We are developing probes that target a wide range of biological processes including gene regulation, mRNA localization, protein expression, and enzymatic activity. Multiple imaging platforms are used including magnetic resonance, fluorescence, and bioluminescence and applications range from studying the complex intracellular dynamics of individual cells to the early detection of disease in a clinical setting.

 

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
Email: vinograd@mail.med.upenn.edu
Vinogradov department 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
Email: wehrlif@uphs.upenn.edu
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
Email: weisel@mail.med.upenn.edu
Weisel Cell and Developmental Biology Web page

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.