tumor cell biology program - Sylvester Comprehensive Cancer Center

Jin, YD, Fuller, L, Wei, YT,
Blomberg, BB, Miller, J and Esquenazi,
V. Bone marrow cells promote TH2 polarization
and inhibit virus-specific CTL
generation. Human Immunology
61:1233, 2000.
Sherwood, EM, Xu, W, King, AM,
Blomberg, BB and Riley, RL. The reduced
expression of surrogate light chains
in B cell precursors from senescent
BALB/c mice is associated with decreased
E2A proteins. Mechanisms of Aging and
Development 118:45, 2000.
HIGHLIGHTS/DISCOVERIES
• Compromised humoral immune response
in aged individuals may be at
least partially explained by antibody V H
repertoire differences at the pre-B cell
level (before antigen selection).
• Breast cancer patients show improved
immune response after psychosocial
intervention.
H. James Hnatyszyn, Ph.D.
Assistant Professor of
Microbiology and Immunology
DESCRIPTION OF RESEARCH
Dr. Hnatyszyn and his research team
are focusing on a number of novel
aspects with regards to cancer detection
and therapeutic interventions. First, they
are incorporating catalytic RNAs, such
as ribozymes and RNAse P molecules,
into strategies for cancer treatment using
gene therapy. They have used these
potent “molecular scissors” to target
tumor-specific oncogenes in leukemias
including BCR-ABL in CML and E2A-
PBX1 in pre-B-ALL. Expression of these
target-specific catalytic RNAs in cancer
cells will reduce the oncogenic message,
thereby rendering the cell more permissive
to conventional therapies and/or permitting
the cancer cell to enter a
regulated replication cycle followed by
programmed cell death. One application
for these interventions is in the purging
of stem cell grafts to remove residual leukemic
cells, reducing the risk of relapse
and making autologous transplantation
a real possibility. Currently they are using
this technology to develop gene
therapies for human leukemias, multiple
myeloma, and solid tumors including
breast, prostate, ovarian, and cervical
cancers.
The second focus of Dr. Hnatyszyn’s
research is to develop rapid, sensitive, and
inexpensive assays for the detection of
human malignancies. It is thought that
early detection and subsequent intervention
improves the prognosis and survival
rate of patients with cancer. In collaboration
with Dr. Gunter Kraus, Dr.
Hnatyszyn’s laboratory utilizes real-time
PCR and highly specific fluorogenic
probes to design and evaluate detection
assays that are very fast (less than 40 minutes),
very sensitive, and rely on very little
material from a patient sample (peripheral
blood, tissue, or bone marrow). In
the past six months, researchers in this
lab have developed a number of rapid
and sensitive assays designed to detect
and identify a number of human malignancies.
These assays can be used for
diagnosis, tumor cell surveillance, monitoring
treatment efficacy, and detection
of residual disease in the patient and in
transplant grafts. They also have expanded
the application of these assays to
encompass infectious diseases (e.g., tuberculosis,
HIV/AIDS) including many
pathogens that may contribute to the
development of human cancers (e.g.,
HHV-8, HPV, HTLV). The speed and
sensitivity of these assays in a clinical setting
will permit clinicians to intervene
early during cancer development and
improve patient prognosis.
PUBLICATIONS
Hnatyszyn, H, Podack, ER, Young,
AK, Seivright, R, Spruill, G and Kraus,
G. The use of real-time PCR and
fluorogenic probes for rapid and accurate
genotyping of newborn mice. Molecular
Cell Probes 15:169, 2001.
HIGHLIGHTS/DISCOVERIES
• Design and development of both hammerhead
ribozymes and RNAse P molecules
that target and effectively cleave
the 1:19 breakpoint observed in some
childhood leukemias.
• Received funding from the Leukemia
Research Foundation to evaluate this
gene therapy in leukemia cell lines and
primary human leukemia cell samples.
Roland Jurecic, Ph.D.
Assistant Professor of
Microbiology and Immunology
DESCRIPTION OF RESEARCH
Since stem cells from various tissues
(bone marrow, intestines, skin, liver,
brain, testis) participate in tissue homeostasis
by replacing differentiated cells lost
to physiological turnover, disease, or injury,
they hold tremendous promise as
model systems for treatment of various
diseases. The lifelong maintenance and
regenerative capacity of the blood cell
forming (hematopoietic) system depend
on self-renewal, lineage commitment,
and differentiation of hematopoietic
stem cells (HSC) and progenitors. Research
conducted in Dr. Jurecic’s laboratory
focuses on 1) elucidation of genetic
mechanisms that regulate the function
of hematopoietic stem cells and development
of blood cell diseases, and
2) analysis of their in vivo developmental
potential. The goal of this research is
to enhance our understanding of HSC
biology in order to achieve successful exvivo
maintenance and genetic manipulation
of HSC for more efficient clinical
stem cell transplantation and gene
therapy of genetic and acquired diseases.
Molecular genetic analysis of HSC
function encompasses identification,
cloning, and functional genetic analysis
of novel genes that regulate blood cell
development and are also involved in leukemogenesis.
They have created and
screened total and subtracted cDNA libraries
from mouse and human HSC and
are also working on creating a stem cell
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002