1: David Wight phone:740-593-4713 fax:740-593-4795 email:wight@ohio.edu Background and interestsDavid
Wight has served as director of the Edison Biotechnology Institute
since 1995. His leadership of the institute is informed by experience
as both a researcher and a business strategist. David’s current areas
of professional interest include transgenic technology and mammalian
gene expression and transfer. 2: Xiaozhuo Chen, Ph.D. phone:740-593-4713 fax:740-593-4795 email:chenx@ohio.edu Research interests My labs major interests in biological and biomedical research include: Genes and protein factors involved in type 2 diabetes (T2D) and obesity (adipogenesis) for insulin resistance.
Insulin resistance is induced by reduced efficiency in insulin
signaling that leads to T2D (Figure 1). The mechanism by which insulin
resistance is produced is not fully known. Increasing insulin signaling
can reduce insulin resistance and improve glucose transport in diabetes
patients. We want to study the roles of different genes and protein
factors in insulin resistance in fat cells (adipocytes).A group of
novel and potent anti-diabetic and anti-adipogenic compounds has
recently been discovered from natural sources in my lab. These
compounds have the potential to become new types of therapeutic
candidates for treating T2D and its associated obesity, one of the
major public health problems in the U.S. The mechanisms by which these
compounds work in glucose transport and in adipogenesis inhibition are
being intensively investigated in both fat cell lines and in diabetic
and obese mouse models. PGG is one of the representative compounds. Genes involved in early development, particularly in vasculogenesis.
Animal cell lines and animals are used for anti-diabetes and
anti-obesity mechanism studies, whereas zebrafish is used for
developmental biology study using reverse genetics approach. These two
seemingly unrelated research projects converge on endothelial cells,
which are negatively affected by hyperglycemia in T2D and abnormally
developed in and around cancer nodules as a part of the blood supply
system. The gene bone morphogenesis protein 4 (bmp4) — which is
traditionally thought to be a ventralization signal in early
development but its other functions are unclear — has been studied
using either a ribozyme-mediated knockdown system or gene
over-expression system. These studies have led to the discovery of new
functions of bmp4 and improve our understanding of its roles in
cardiovascular diseases and in cancer. Endothelial cells will be used
as a new model for future study. 3: Susan C. Evans, Ph.D. phone:740-597-1319 fax:740-593-4795 email:evanss1@ohio.edu Research interests My
primary research interest focuses on the scientific understanding of
what influences an individuals risk of cancer. One hypothesis suggests
that the risk of cancer is determined by the inheritance of cancer
resistance or susceptibility genes, which are referred to as "genetic
modifiers." My goal is to identify these cancer-modifying genes.The
tumor suppressor gene, p53, is mutated in over 60% of all human tumors.
My research focuses on the p53 tumor suppressor pathway in cancer and
development, in particular how p53 function is affected by genetic
modifiers or DNA damage. The identification of p53 risk modifiers as
well as the essential players in its pathway will have important
implications - not only for the fundamental biology of cancer and
development, but also for preventing, diagnosing and treating malignant
tumors.My laboratory colleagues and I pursue many related research
projects, including: Discovering the gene responsible for an embryonic lethal phenotype.
We are using mice as a model system to discover genetic modifiers of
the tumor suppressor p53. In CE/129 mice with a p53 mutant allele,
approximately a third of them die during gestation. The embryos have
brain malformations and are smaller in size than their littermates. We
have mapped to loci linked to the phenotype and are in the process of
determining the gene within these loci that cause the lethal event.
This study will give information as to human development and birth
defects. Discovering novel tumor suppressors.
Using mice as a model, we are searching for genes involved in
predisposition to cancer, tumor onset, and metastasis using simple
sequence length polymorphism analysis of tumors. We have identified a
candidate locus and are now in the process of discovering the gene. The
identified tumor suppressor could be used as a target for gene therapy. Discovering novel synthetic compounds.
We are testing synthetic compounds for radiosensitivity of tumor and
normal cells. These could be used as a therapeutic in conjunction with
radiation for the treatment of cancer. Determining molecules that cause proliferation of stem cells for the regeneration of intestine after radiation.
Using a proteomic and genomic approach, we will identify genes and
proteins that help to regenerate normal mucosa which have been highly
damaged after radiation treatment of tumors. These molecules may be
used to protect the normal cells from radiation damage during therapy. Characterizing an alternative splice product of HDM2.
HDM2 is the negative regulator of the tumor suppressor p53. Recently we
have found that it is spliced after DNA damage. We also have discovered
that the spliced form (ALT) binds full-length HDM2 and prevents its
negative regulation of p53. We are further characterizing this molecule
using transgenic mice and performing in vitro studies. It has the
potential to be used as a therapeutic in cancer treatment to keep p53
active so that it can cause cell cycle arrest and cell death, and also
as a diagnostic marker for cancer. 4: Leonard D. Kohn, M.D. phone:740-593-4587 fax:740-593-4795 email:kohnl@ohio.edu Research interests My
group and I focus on how autoimmune disease begins — the mechanism of
onset, particularly of endocrine autoimmunity (Graves disease,
diabetes). Our goal is to discover new drugs for treatment of these
conditions.We also study regulation of the growth and function of the
thyroid and the basis for self-tolerance. Then we evaluate the
mechanism of transcriptional regulation of MHC gene expression and its
link to hormonal regulation and self-tolerance.Our projects in
collaboration with academic and business partners include: Drug development for treating autoimmune disease.
A potential "lead" agent useful in treating autoimmune problems in
systemic lupus and Type 1 diabetes has been identified based on in
vitro and in vivo studies. Drug
development for treating inflammatory disease associated with increases
in adhesion molecule gene expression and leukocyte adhesion.
The agent in the above-mentioned program has been shown to selectively
inhibit VCAM-1> E-selectin but not affect ICAM-1 in human arterial
endothelial cells (HAEC). It inhibits leukocyte binding to HAEC and
does this in a novel manner: inhibition of IRF-1 gene expression. The
drug has been tested in a disease model, DSS-induced colitis, and shown
to be efficacious. The agent thus has both anti-inflammatory and
anti-immune properties. A related model evaluating its in vivo action
in atherosclerosis and vascular complications of diabetes, which has a
pathogenic basis similar to colitis, will be evaluated. Drug development for treating innate immunity.
The agent in the aforementioned programs has been found to be effective
in blocking innate immune responses involved in disease development,
such as toxic shock. Its usefulness in vivo has been established in
mice. Diagnostics.
Improved methods to measure thyrotropin receptor autoantibodies, using
transfected cells with chimeric receptors, have been developed. They
are being beta tested in clinical settings and for production assays. Clinical data base and tissue repository.
A clinical data base and repository for endocrine disease, with a
primary focus on diabetes and its complications, has been established.
The results are of potential interest to drug companies and other
commercial partners. 5: John J. Kopchick, Ph.D. phone:740-593-4534 fax:740-593-4795 email:kopchick@ohio.edu Research interestsMy
group and I focus on the molecular biology of growth, obesity, insulin
resistance, diabetes, and aging. All of our projects use animal models
and a proteomics approach to investigate and understand the molecular
and cellular events leading to the onset and progression of diseases
and the aging process. The goal is to discover biomarkers which can be
developed into therapeutics, therapeutic targets, and diagnostics.An
understanding of the molecular basis of growth hormone (GH) action is
important, since GH is currently used as a human therapeutic and as a
milk production enhancer in animals. The long-term goal of my
laboratory is to identify signaling intermediates in GH responsive
tissue in vivo.An approach to this problem has been to generate
transgenic mice that express GH or GH antagonists, a new class of human
therapeutics discovered in our laboratory. We also use a gene
disruption approach. In this case we have "knocked" out the GH receptor
gene. The resulting animals are dwarf. Using these models, we evaluate
biochemical, endocrine, and physiological properties of these animals
and identify signaling intermediates in GH responsive tissue. Also, we
use these animals to determine the combined effects of GH and GH
antagonists in diabetes-induced end-organ damage. We have recently
shown that GH antagonists protect mice from diabetes-induced
nephropathy.
Professional activities and membershipsEditorial boards
Journal of Biological Chemistry, June 1995 to 2000
Endocrinology, January 2003 to present
Growth Hormone and IGF Research, January 2003 to present
Molecular Endocrinology, January 2001 to presentProfessional organizations
American Association for the Advancement of Science
The American Society for Biochemistry and Molecular Biology
American Society of Microbiology
Endocrinology Society
Growth Hormone and IGF-1 Society
Phi Kappa Phi
Pituitary Society
Sigma Xi 6: Shiyong Wu, Ph.D. phone:740-597-1318 fax:740-593-4795 email:wus1@ohio.edu Research interests Many
human diseases - such as viral infection, diabetes, obesity and cancer
- are related to misregulation of translation initiation and
endoplasmic reticulum (ER)-stress. My studies are intended to clarify
the regulatory signaling pathways of translation initiation and
ER-stress, and to identify target genes for drug discovery and disease
treatment.Specifically, my research focuses on the regulation of
eukaryotic protein synthesis initiation and endoplasmic reticulum
(ER)-stress. Phosphorylation of the a-subunit of the eukaryotic
initiation factor 2 (eIF2a) is a fundamental mechanism that regulates
the rate of protein synthesis as cells respond to their external
stimuli. Stresses, such as UV, growth factor depletion, hypoxia, viral
infection and ER stress, rapidly inhibit protein synthesis through
phosphorylation of eIF2a. Most of these stress-induced eIF2a
phosphorylations are mediated by PKR and PERK. I have elucidated the
mechanism for PKR activation and identified novel signaling pathways
that lead to translational inhibition and NFkB activation after
UV-irradiation.My laboratory colleagues and I pursue many related
research interests, including: Viral infection.
Elucidation of the mechanism that translationally regulates Human
Papillomavirus (HPV) E6/E7 expression. Development of diagnostic system
for screening chemicals that regulates translation initiation. The
identified chemicals may be used for treatment of viral infection. Multiple myeloma (MM) and some other cancers.
Identification of target gene for MM treatment. Development of
diagnostic system for screening chemicals that affect endoplasmic
reticulum (ER)-stress level. The identified chemicals may be used for
treatment of MM and some other cancers. UV-related skin cancer.
Elucidation of signaling pathways for UV-induced translation
regulation, ER-stress, NFkB activation and apoptosis. These studies
will lead us to the identification of target genes and future
development of drugs for prevention or treatment of UV-related skin
cancer. Immune stimulant.
Investigation of the mechanisms and effects of two natural biological
response modifiers (BRM). Development of cell culture systems for
activity assay of the BRMs. These studies will lead us to introduce
these anti-infectious peptides to the US market. | 
