PENN-PORT Fellows and Staff at the 2008 Annual IRACDA Conference held at UNC Chapel Hill
Program Staff
LaShauna Myers Connell, Recruitment Coordinator
Yvonne Paterson, Ph.D., Principal Investigator
PENN-PORT Fellows- 2007-2008
Marcel Estevez, Ph.D.
Meda Higa, Ph.D.
James Munoz, Ph.D.
Cinque Soto, Ph.D.
Audria Stubna, Ph.D
Angel Varela- Rohena, Ph.D.
Marcel Estevez, Ph.D.
mestevez@sas.upenn.edu
Education
Ph.D. Cellular and Molecular Medicine, Johns Hopkins University School of Medicine
Mentor
Ted Abel, Ph.D.
Research
Synaptic plasticity refers to the mutability of synaptic strength, and is considered the basis for learning and memory, as well as other paradigms, such as addiction. My interests lie in understanding the activity-dependent mechanisms for the modulation of synaptic strength. In particular, I am interested in how transcription mediates long-term changes in synaptic strength.
Long-term potentiation (LTP) is a long-term increase in synaptic strength. As histone acetylation has been shown to enhance LTP, we are studying the role of histone acetyl-transferases (HATs), such as CBP and p300, and histone deacetylases (HDACs), in modulating the synaptic response. In our studies we are looking at LTP in the Schaffer collateral of the mouse hippocampus; and we use genetic and pharmacological approaches to alter HAT and HDAC activity. Some of the target genes for CBP are orphan nuclear receptors, namely NGFI-B and Nurr1. Also, acetylation modulates retinoic acid signaling, which also implicates nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Consequently, we also want to study the role of nuclear receptors in transcriptional processes that mediate LTP.
Meda Higa , Ph.D.
mhiga@mail.med.upenn.edu
Education
Ph.D. Oncological Sciences, University of Utah
Mentor
Bob Doms, M.D, Ph.D.
Research
My postdoctoral research focuses on the cell biology of Hantaviruses in the family Bunyaviridae. Hantaviruses are rodent-born viruses that can be transmitted to humans and result in two highly pathogenic diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The objectives of my research are to better understand the cellular interactions of Sin Nombre Virus and Puumala Virus. My specific aims are to further characterize the mechanism of cell entry, understand viral cell tropism, and identify host protein interactions with the viral glycoproteins Gn and Gc.
Puumala Virus (PUUV) and Sin Nombre Virus (SNV) are members of the genus Hantavirus (family Bunyaviridae). In humans, virus infection results in the diseases Hemorrhagic Fever with Renal Syndrome (HFRS) or Hantavirus Pulmonary Syndrome (HPS), respectively. Mortality rates can be up to 50% with SNV. Hantaviruses are usually transmitted via inhalation of excreta from the natural host rodent. Although early diagnosis and aggressive supportive care improve patient survival, there are currently no approved antiviral drugs or vaccines available. PUUV and SNV have single, negative-sense trisegmented RNA genomes. The medium (M) segment encodes the envelope glycoproteins, GN and GC, that accumulate in the Golgi, where new virus budding normally occurs. These glycoproteins promote cell attachment and fusion of virus and endosomal membranes, although the roles of GN and GC in receptor binding and cell fusion have not been well characterized. To address more specifically the role of PUUV and SNV glycoproteins in viral entry in a BSL2 setting, we have adapted the technique of pseudotyping hantavirus glycoproteins onto a Vesicular Stomatitis Virus (VSV) core. We have successfully expressed codon-optimized PUUV and SNV M segments in 293T cells and infected with VSVDG*rLuc, resulting in single-round infectious pseudotypes. These pseudotypes are specifically neutralized with glycoprotein antibodies, and infection characteristics are similar to that seen with wild-type virus. Work is currently underway to further elucidate the role of PUUV and SNV glycoproteins in cell entry and infection.
James Munoz, Ph.D
munozjam@mail.med.upenn.edu
Education
Ph.D. Neuroscience, Tulane University
Mentor
Matthew Dalva
, Ph.D.
Research
I am interested in examining how intrinsic and extrinsic factors regulate neural progenitor cell (NPC) development. I have been examining how IP3-mediated calcium signaling affects the development of NPCs and how cortical astrocytes regulate their differentiation. I have recently begun studying the role of the synaptogenic molecule EphB2 in endogenous NPCs. To accomplish these studies, I have been using modern, commonly used techniques such as the isolation and culture of neural progenitor cells, lentiviral transduction, pharmacology, siRNA, shRNA, confocal and 2-photon microscopy. By focusing on the intrinsic and extrinsic factors regulating NPCs, we have the opportunity to understand mechanisms that regulate developmental maturation and cellular integration into existing adult neural circuits.
Cinque Soto, Ph.D.
cinques@mail.med.upenn.edu
Education
Ph.D. Biochemistry and Molecular Physics, Columbia University
Curriculum Vitae
Mentor
Bill Degrado, Ph.D.
Research
My research interests center around the use of molecular biophysics and structural bioinformatics as tools to understanding molecular disease. Frequently, membrane protein structure cannot be elucidated using standard techniques like X-ray diffraction or NMR spectroscopy. In these situations, comparative modeling methods can provide low resolution structural information. The resolution (and accuracy) of the model can be improved by incorporating experimental information into the modeling process. My current focus is to develop novel methods of incorporating experimental information into the modeling process. For example, I have recently developed a method for incorporating disulfide-cross linking data into elucidating the physiological interface of the PhoQ protein.
My overall goal is to develop a suite of computational methods that can be used in de novo protein design and structure prediction. Currently, I am focusing on extending homology modeling methods so that they can be applied to computational protein design. As a first step toward this goal, I have begun developing a protein conformational sampling algorithm that can incorporate external restraints derived from cross-linking experiments or spectroscopic methods such as EPR and IR. Modifications of the sampling algorithm are currently being used to provide protein backbone flexibility in computational drug design.
Audria Stubna, Ph.D
stubna@mail.med.upenn.edu
Education
Ph.D. Chemistry, Carnegie Mellon University
Mentor
Les Dutton, Ph.D.
Research
Trained in Mössbauer and electron paramagnetic resonance spectroscopies, I seek to apply my knowledge of bioinorganic systems to research more geared toward undergraduate involvement. I have successfully shifted from physics based research built on strong collaborations with various chemistry and biochemistry departments to synthetic biochemistry. My current research involves the study of light-activated electron transfer using synthetic proteins.
Simple yet robust synthetic proteins are prefect for studying biological electron transfer processes. The idea is to remove more complicated functions which are typically present in biological proteins, making it possible to identify more clearly the factors controlling electrochemical reactions. Synthetic proteins used are designed similarly to the the four α-helix scaffolds designed first in the laboratory of Bill DeGrado and developed further by P. Leslie Dutton. Metal cofactors such as iron porphyrin and zinc protoporphyrin-IX are bound to these maquettes to allow for light-activation and reduction/oxidation capabilities. As the functionality is built up from simple electron transfer to include light-activation, significant charge separation can be achieved in a single molecule. Using such proteins to sensitize titianium oxide coated electrodes leads to a non-conventional solar cell which lacks inefficient cofactor aggregation. While this remains a costly alternative for harnessing solar power, the working protein scaffold has an added capability of building on the functionality of a reactive amino acid or other catalytically active center which are currently being developed in the Dutton Lab. Ideally the end function is a fuel cell, using solar energy to convert, for example, water into oxygen and hydrogen gases.
Angel Varela-Rohena, Ph.D.
varelaa@mail.med.upenn.edu
Education
Ph.D. Immunology, University of Pennsylvania
Curriculum Vitae
Mentor
Jim Riley, Ph.D.
Research
Research Project: Generation of high-affinity antigen-specific T cells for adoptive immunotherapy Unlike B cells, T lymphocytes have a relatively low avidity for their cognate antigen. Low avidity may represent a compromise that allows T cells to respond to foreign peptides while remaining tolerant to self. While previous studies indicate that CTLs exhibiting high avidity for their cognate antigen are more effective in clearing virus or tumors and are preferentially selected for in the memory population, it is uncertain whether T cells function because of, or in spite of, their low TCR affinity for cognate antigen. We have developed a human TCR transgenic model that allows us to study whether T cells responses can be enhanced by TCRs with antibody-like affinity. We have developed two model systems with the following antigens:
HIV p17gag: TCRs differing in affinity for the HIV p17gag epitope SL9 (SLYNTVATL) were introduced into primary human CD8 T cells and the ability of these cells to produce cytokines and to control HIV infection in vitro is proportional to their relative TCR affinity for antigen. We are currently studying whether high-affinity TCR-transduced T cells can control HIV in an in vivo model of HIV infection using huNOG-SCID mice.
Human TERT (hTERT): The human telomerase reverse-transcriptase (hTERT) is an attractive target for cancer immunotherapy due to its crucial role in tumor survival and its limited expression in normal adult tissues. We are currently studying a high-affinity hTERT-specific TCR. When introduced into primary T cells we can generate potent effector cells that can recognize HLA-A*02+/telomerase+ tumor cell lines.
© The Trustees of the University of Pennsylvania | Template Design: SOMIS Web Team