Amelia E. Hufford
Ph.D. in Microbiology, May 2013
"Phosphatidylserine recognition receptors: promoters of muscle
development and apoptotic cell engulfment"
In the laboratory of Dr. Kodi Ravichandran, Amelia’s thesis research
focused on understanding the role of the phosphatidylserine (PtdSer)
receptor, BAI1, and apoptotic cells in muscle development and repair.
Myoblasts are muscle progenitor cells that must fuse with one another
during muscle development to form multinuclear myofibers. Amelia
demonstrated that BAI1 expression in myoblasts positively regulates
myoblast fusion, which is dependent on the activation of the
ELMO/Dock180/Rac signaling pathway. In vivo, myofibers from
Bai1-/- mice are smaller than wild-type littermates,
and muscle regeneration after injury was also impaired in
Bai1-/- mice, highlighting a role for BAI1 in
mammalian myogenesis. Amelia further observed that during myoblast
fusion, a fraction of myoblasts undergo apoptosis and expose PtdSer, an
established ligand for BAI1. Moreover, she determined that blocking
apoptosis potently impairs fusion, and adding back apoptotic myoblasts
restores fusion. Finally, primary human myoblasts could be induced to
form myotubes by adding apoptotic myoblasts, even under normal growth
conditions. Together, these findings identify BAI1 and apoptotic cells
as novel promoters of myoblast fusion, with significant implications
for muscle development and repair.
Ph.D. in Microbiology (Fall 2012)
"Purine acquisition and biosynthesis in Helicobacter
George works with the bacterium Helicobacter
pylori, a causative agent of gastritis, duodenal ulceration,
and gastric cancer. He is currently investigating the purine salvage
pathway in H. pylori with the goal of fully
elucidating the essential enzymes required for maintaining the
bacterium’s nucleotide pool. Its inability to synthesize purines
de novo makes key enzymes in this pathway attractive drug
targets for future antimicrobials.
Matthew T. Hufford
Matthew T. Hufford
Ph.D. in Microbiology (Spring 2011)
"Regulation of Cytotoxic T Lymphocytes Effector Function During
Experimental Murine Influenza Infection"
Matthew's thesis research focused on the regulation of cytotoxic T
lymphocyte (CTL) effector function during murine influenza infection.
He demonstrated that indeed CTLs could recognize infected respiratory
epithelial cells and destroy the cells but that this T cell/target cell
interaction did not lead to release of pro-inflammatory cytokines. By
contrast, CTLs also interacted with influenza antigen displaying CD45+
inflammatory cells in the infected lung interstitium. It is this
interaction that not only leads to destruction of the cells but to the
production of pro-inflammatory cytokines by the CTLs. He further
demonstrated that this regulation of T cell effector activity is
dependent in part on the presence or absence of co-stimulatory
molecules on the targeted cell. These findings have important
implications for the development of pulmonary inflammation /injury and
"cytokine storm" during severe influenza infection.
Judy White Lab
Ph.D. in Microbiology, Spring 2010
"Ebolavirus Entry: Cell adhesion-dependent control of viral
In the laboratory of Dr. Judith White, Derek's work has focused on
the initial stage of viral entry. Employing cell culture systems, Derek
recognized a role for cellular adhesion in the regulation of ebolavirus
tropism. He showed that cells that grow in suspension (including
lymphocytes) formerly thought to lack an ebolavirus receptor actually
sequester a receptor intracellularly, and provided evidence that upon
cell adhesion the receptor can be translocated to the cell surface.
These results revealed a novel means of regulating viral tropism that
is likely of pathological importance for ebolavirus infection. Derek
has presented his work at two meetings of the American Society of
Virology and, to this point, is the first author on two, and co-author
on two, published studies.
Anna Maria Copeland
Jay Brown Lab
Ph.D. in Microbiology May 2009
Herpes Simplex Virus Replication: Roles
of Viral Proteins and Nucleoporins in Capsid-Nucleus Attachment.
herpes simplex virus (HSV-1) involves a step in which a parental capsid
docks onto a host nuclear pore complex (NPC). The viral genome then
translocates through the nuclear pore into the nucleoplasm where it is
transcribed and replicated to propagate infection. We have developed a
live cell system to study the interaction between the herpes capsid and
the host NPC in the context of an infection. Using the live system, we
investigated the roles of viral and cellular proteins in the process of
capsid-nucleus attachment. Our results suggest that the viral tegument
protein VP1/2 is involved in specific attachment to the NPC and/or in
migration of capsids to the nuclear surface. Results indicate cellular
Nup358 is required for nuclear capsid binding, possibly serving as the
nuclear receptor for herpes capsids. We are currently working to
identify a capsid binding domain within Nup358.
Michelle L. Demory
Sarah J. Parsons Lab
Michelle L. Demory
Ph.D. in Microbiology May 2008
Investigation of the regulators of
epidermal growth factor receptor translocation to the mitochondria and
determination of the impact of EGFR association with the mitochondrial
protein Cytochrome c Oxidase Subunit II
utilized a cell model system that mimics late stage breast cancers by
co-overexpressing epidermal growth factor receptor and c-Src. We found
that EGFR can transiently translocate to the mitochondria where it can
associate with the mitochondrial protein cytochrome c oxidase subunit
II. Our results suggested this translocation is regulated by a
multifaceted regulatory mechanism utilizing clathrin-mediated
endocytosis, c-Src and a mitochondria localization sequence.
Furthermore, we showed that EGFR can directly phosphorylate CoxII and
that EGF stimulation can increase mitochondrial potential and Cox
Dean Kedes Lab
Ph.D. in Microbiology August 2007
Single cell characterization of kaposi's
sarcoma-associated herpesvirus infection: tropism, immune evasion, and
infection is a hallmark of all herpesviruses, and their survival
depends on countering host immune defenses. The human γ-herpesvirus
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes an array of
proteins that contribute to immune evasion, including Modulator of
Immune Recognition 2 (MIR2), an E3 ubiquitin ligase. Our results
suggest that the effects of MIR2 are gene dosage dependent and that low
levels of this viral protein contributes to the widespread
downregulation of immune modulating cell-surface proteins during the
initial stages of KSHV infection.
Michael W. Cruise
Young Hahn Lab
Ph.D. in Microbiology Fall 2005.
Enhanced FASL Expression by HCV Core Induces the Production of
CXCR3 Chemokines and Liver Damage
Mike was involved in studying Fas/FasL
interaction in liver inflammation in hepatitis C virus (HCV) infection.
Using transgenic mice expressing the HCV core protein, Mike studied the
recruitment of activated T cells to the liver and the mechanism of
damage by liver infiltrating lymphocytes. He found that expression of
HCV core protein in T cells enhanced the level of FasL. Michael Cruise
is currently finishing up his MD degree here at UVa and plans on a
residency in pathology.
Joanna Goldberg Lab
Ph.D. in Microbiology Fall 2005.
Protection from Pseudomonas Aeruginosa Pneumonia After Vaccination
with Recombinant Live Attenuated Salmonaella: Correlates of Protective
Immunity in the Respiratory Tract
Vanderbilt University Medical Center
Department of Microbiology & Immunology
My research is focused on the development
of recombinant cell penetrating (CP) suppressor of cytokine signaling
(SOCS) proteins that can be therapeutically used to inhibit excessive
inflammation in a murine model of acute lung injury.
I hypothesize that therapeutic supplementation of intracellular stores
of these inhibitory molecules will prevent or lessen the deleterious
effects of excessive inflammation in the lung and could have major
implications for individuals who are stricken with bacterial pneumonia
and suffer unwarranted levels or morbidity.
Lucy Pemberton Lab
|Nima Mosammaparast, M.D., Ph.D.
Ph.D. in Microbiology Spring 2005.
Core Histone Nuclear Transport: Mechanisms and links to Chromatin
Clinical Pathology Resident 2006 to present
Brigham and Womens' Hospital
Nima's research has focused on the
molecular mechanism via which distinct nuclear transport factors, also
called karyopherins, import chromatin components including histones
into the nucleus. He has extended this work to look at how nuclear
import may interface with other nuclear processes such as chromatin
Kodi S. Ravichandran Lab
Li Zhang, Ph.D.
Ph.D. in Microbiology Fall
Genetic studies of Shc function in T cells
Department of Molecular Biology and Genetics
School of Medicine
Johns Hopkins University
In an attempt to understand the role of Shc
during T cell development, so we constructed a conditional transgenic
mouse that expresses a dominant-negative (phosphorylation-defective)
form of Shc confined to the T cell lineage. After we showed expression
of the Shc isoform, we have advanced studies to understand effects on
proliferation, differentiation, and even thymic maturation, proving
that Shc phosphorylation plays an essential and non-redundant role in T