California
Cancer Research Program
Completed Projects
The following Principal Investigators have completed
their research as funded by CRP. Where applicable, publications resulting from
CRP funding are also included.
CYCLE II FINAL
LAY ABSTRACTS
Investigator Initiated Award
Robert J, Debs, Ph.D.: Systemic Gene Therapy for Metastatic Prostate Cancer
Alan L.
Epstein, M.D., Ph.D.: chTNT-3/IL-2: A
New Fusion Protein for the Treatment of Solid Tumors
John J.
Krolewski, M.D., Ph.D.: The Role of
FLIP in Prostate Epithelial Cell Apoptosis
Kit S. Lam,
M.D., Ph.D.: Experimental Therapeutics
of Ovarian Cancer with Peptides
Shoshanna
Levy, Ph.D.: Hepatitis C Virus (HCV) -
Associated Lymphomas
Francis S.
Markland, Ph.D.: Anti-Invasive and
Anti-Angiogenic Therapy for Ovarian Cancer
Dan
Mercola, M.D., Ph.D.: Innovative
Treatment of Prostate Cancer - Antisense Jun Kinase
Ralph A. Reisfeld, Ph.D.:
Novel Therapies for the Treatment of Colon
Cancer
Sidney S. Sobin, Ph.D., M.D.:
Urinary Bladder Angiogenesis in Bladder
Cancer Diagnosis
Eri S.
Srivatsan, Ph.D.: Cervical Cancer Tumor Suppressor Gene from
Chromosome 11q13
Luis
P. Villarreal, Ph.D.: Therapy
of HPV Mediated Cervical Cancer in a SCID Mouse
New Investigator Award
Chisa Aoyama, M.D.: FSH as a Key Growth Promoter in Ovarian Epithelial
Tumorigenesis
Michael Bouvet, M.D: Novel Gene Therapy Strategies for Pancreatic Cancer
Robert A. Burger, M.D.: Impact of Tumor Formation on Ovarian Cancer Spread
Genhong Cheng, Ph.D.: Novel Antagonist Treatment for Nasopharyngeal
Carcinoma
Hanna Damke, Ph.D.: Dynamin-2, a Novel Target for Cancer Therapy
Kenan C. Garcia, Ph.D.: Structural Studies of Interleukin-6 as an
Anti-Cancer Target
Shuang Huang, Ph.D.: Ribozyme-Mediated Adenovirus Gene Therapy in Ovarian
Cancer
Carla M. Koehler, Ph.D.: Protein Import into Mitochondria and the Link to
Cell Growth
John Love, Ph.D.: New Compounds for the Treatment of Ovarian Cancer
Clifford G. Tepper, Ph.D.:
Molecular Profiling of Protein Tyrosine
Phosphatases in Prostate Cancer
Pilot and Feasibility Award
Gary M. Bokoch, Ph.D.: Regulation
of Angiogenesis by p21-Activated Kinases
Miles C. Cabot, Ph.D.: Targeting Ceramide to Treat Prostate and Ovarian
Cancer
Steve Goodison, Ph.D.: Bladder Cancer Detection by Quantitative Telomerase
Analysis
Kim D. Janda, Ph.D.: Cancer Therapy Using Human Antibodies
Ulla G. Knaus, Ph.D.: The Role of Reactive Oxygen Species (ROS) in Ovarian
Cancer Metastasis
Kenneth J. Longmuir, Ph.D.:
A Next-Generation Gene Delivery System for
Cancer Therapy
Anson W. Lowe, M.D.: Specific Gene Expression in Human Pancreatic Cancer
Stephen J. Pandol,
M.D.: Regulation of Pancreatic Cancer
Apoptosis by Polyphenols
Francisco J. Piedrafita,
Ph.D.: Inhibition of NFκB by
Apoptotic Retinoids in Prostate
Sherven Sharma, Ph.D.: Immunotherapy for Prostate Cancer
Masato Tanabe, Ph.D.: Innovative Treatment of Hormone Refractory Prostate
Cancer
Jose V. Torres, Ph.D.: Vaccine against Human Papillomavirus
Luis P. Villarreal,
Ph.D.: Polyomaviruses and Prostate
Cancer in a SCID Mouse Model
Kristiina Vuori, M.D., Ph.D.:
Cell Adhesion and Drug Resistance in
Ovarian Cancer
Heinz-Ulrich G. Weier, Ph.D.: Tyrosine Kinase Expression Profiling in Prostate
Cancer
Nurulain Zaveri, Ph.D.: Antiangiogenic Agents for Prostate Cancer Therapy
Postdoctoral Fellow Award
Wenteh Chang, Ph.D.: The p53 Pathway in Triptolide-Induced Tumor Cell
Apoptosis
Siska I. Corneillie,
Ph.D.: Insights into the Mechanism of
p53-Dependent Transcription
Shane Donovan, Ph.D.: Growth Factor Hypersensitivity in Myeloid Leukemia
Katherine B. Ellwood, Ph.D.:
PTEN Regulation of the C-MYC Pathway in
Prostate Cancer
Anjali Jain, Ph.D.: Prostate
Stem Cell Antigen as a Novel Tool for Gene Therapy
Steven J. Kridel, Ph.D.: The Protease Profile of Prostate Cancer
Laurence Lamarcq, Ph.D.: The Role of HPV16 E7 Mediated Events in Cervical
Disease
Sun Paik, Ph.D.: Prostate Cancer Eradication by Tissue Specific Gene
Therapy
Shalini E. Pereira, Ph.D.:
Progression of Leukemia in Mice Lacking
Intracellular Signaling Molecules
Mallika Singh, Ph.D.: The Role of Angiogenic Factors in the Progression of
Squamous Cell Carcinoma
Helene C. Vervoort, Ph.D.:
Targeting Natural Product Cytotoxins to
Tumor Vasculature
Small Business Award – Phase I
Desmond D. Mascarenhas,
Ph.D.: IGF-Binding Protein for the
Treatment of Prostate Cancer
Meng Yang,
M.D., Ph.D.: Bone Metastases in
Prostate Cancer
Xiao-Dong
Yang, M.D., Ph.D.: A Human Antibody
for the Treatment of Prostate Cancer
Hui Zhao,
M.D., D.M.D.: New Anticancer
Angiogenesis Inhibitor from Human Urine
ABSTRACTS
Gary M. Bokoch, Ph.D.
The Scripps Research
Institute
$252,653 / 24 months
Pilot and Feasibility Study Award
General Cancer
A person’s blood vessels deliver
life-saving oxygen and nutrients to all parts of the body. Like the body itself, the ability of
prostate tumors to grow and spread requires that they develop their own blood
supply. Recent studies have shown
that if this blood supply is disrupted, the prostate cancer cells will
die. It is therefore important to
understand the processes that lead to blood vessel formation by prostate tumors
and to determine how we can regulate them.
We are studying the role of a
protein called PAK in blood vessel development. We have shown that PAK regulates changes in cell structure
that allow them to change shape and move.
Our current work has shown this to also be true in the specialized
"endothelial" cells that form blood vessels. We have now established that PAK
activity is required for normal endothelial cell movement and to form blood
vessel precursors. We have
evaluated how certain agents that stimulate endothelial cells to form blood
vessels activate PAK. Over the
past year, we have identified molecules that determine when and where PAK will
localize in cancer cells and other cell types. We have also identified a new PAK-interacting protein that
may allow PAK to communicate with angiogenic stimulators. Our ongoing work is
directed at trying to fugure out how PAK regulates blood vessel formation at a
molecular level.
Since one way to test whether PAK
is important in controlling blood vessel formation is to increase or decrease
its normal activity in cells, we are exploring ways to introduce proteins into
live cells that will do this. We
have made progress in generating protein inhibitors that effectively enter live
cells and affect PAK activity. We
plan to further improve this system for eventual use in cell and / or animal
model systems.
1. Schrantz N, da Silva Correia J, Fowler B, Ge , Sun,
and Bokoch GM (2004) Mechanism of p21-activated Kinase 6-mediated
Inhibition of Androgen Receptor Signaling. J Bio Chem, 279 (3),
1922-193
2. Stofega MR, Sanders LC, Gardiner EM, Bokoch GM (2004) Constitutive p21-activated kinase (PAK)
activation in breast cancer cells as a result of mislocalization of PAK to
focal adhesions. Mol Biol Cell. 6:2965-77. Epub 2004 Mar 26.
Novel
Gene Therapy Strategies for Pancreatic Cancer
Michael Bouvet, M.D.
University
of California, San Diego
$322,097 / 36 months
New Investigator Award
Pancreatic
Cancer
Pancreatic cancer is the fourth
leading cause of adult cancer deaths in the United States. An estimated 29,000 new cases of
adenocarcinoma of the pancreas will be diagnosed in the US and 28,900 patients
will die of this aggressive malignancy each year. Only 1 to 4% of all patients diagnosed with pancreatic
cancer can expect to survive 5 years.
Pancreaticoduodenectomy with adjuvant chemoradiation is the current
standard of care for patients with resectable pancreatic adenocarcinoma;
however even with such treatment, the median survival is less than 2
years. Clearly, new treatment
modalities must be established to combat this disease.
Recent progress in vector
development has made adenoviral-mediated gene therapy a promising approach to
cancer treatment. Gene therapy
strategies aim to restore the wild-type form of mutated genes. Sporadic cancers of the pancreas are
frequently associated with the activation of an oncogene, K-ras, and the
inactivation of multiple tumor suppressor genes, including p53, DPC4, p16, and
Rb. Given the increasing knowledge
of the genetic abnormalities that make up pancreatic cancer, gene therapy is
the next logical step for active translational research programs focused on
this lethal disease.
The aims of this project are 1) to
determine the ability of gene therapy to halt the growth of human pancreatic
cancer in cell culture, 2) to develop a new mouse model of pancreatic cancer
that will help test new treatment strategies, and 3) to determine the effects
of gene therapy in the new mouse model.
To date, we have begun testing
gene therapy strategies against pancreatic cancer in our laboratory. Our preliminary data show that several
of these gene therapy strategies halt the growth of pancreatic cancer by
inducing apoptosis, or programmed cell death. We have developed a new mouse model of pancreatic cancer
that expresses a green-fluorescent protein to aid in detection of tumor growth
and metastases. The advantage of
this model is that tumor growth can be assessed without the need for surgery or
sacrifice of the animal. We have
tested several of these gene therapy strategies in our mouse model of
pancreatic cancer and have had promising results.
1. Katz MH, Spivack D, Takimoto S, Fang B, Burton DW,
Moossa AR, Hoffman RM, Bouvet M.
Gene therapy of pancreatic cancer with GFP-TRAIL fusion gene expression
driven by a human telomerase reverse transcriptase promoter. Annals of Surgical Oncology
10(7):762-772, 2003.
2. Katz MH, Takimoto S, Spivack D, Moossa AR, Hoffman RM,
Bouvet M. A Novel Red Fluorescent
Protein Orthotopic Pancreatic Cancer Model for the Preclinical Evaluation of
Chemotherapeutics. Journal of
Surgical Research 113:151-160, 2003.
3. Katz MH, Bouvet M, Takimoto S, Spivack D, Kobayashi T,
Moossa AR, Hoffman RM. Selective
antimetastatic activity of cytosine analog CS-682 in a red fluorescent protein
orthotopic model of pancreatic cancer.
Cancer Research 63:5521-5525, 2003.
4. Katz MH, Bouvet M, Takimoto S, Spivack D, Moossa AR,
Hoffman RM. Survival efficacy of
adjuvant cytosine-analogue CS-682 in a fluorescent orthotopic model of human
pancreatic cancer. Cancer Res.
2004 Mar 1;64(5):1828-33.
5. Katz MH, Takimoto S, Spivack D, Moossa AR, Hoffman RM,
Bouvet M. An imageable highly
metastatic orthotopic red fluorescent protein model of pancreatic cancer. Clin Exp Metastasis. 2004;21(1):7-12.
6. Bouvet M, Yang M, Nardin S, Wang X, Jiang P, Baranov
E, Moossa AR, and Hoffman RM
(2000) Chronologically-specific metastatic targeting of human pancreatic
tumors in orthotopic models. Clin Exp Metastasis 18:213-8.
7. Lee NC, Bouvet M, Nardin S, Jiang P, Baranov E,
Rashidi B, Yang M, Wang X, Moossa AR, and Hoffma RM (2000) Antimetastatic efficacy of adjuvant gemcitabine in a
pancreatic cancer orthotopic model. Clin Exp Metastasis 18:379-84.
8. Bouvet M, Wang J, Nardin SR, Nassirpour R, Yang M,
Baranov E, Jiang P, Moossa AR, and Hoffman RM (2002) Real-time optical imaging of primary tumor growth and
multiple metastatic events in a pancreatic cancer orthotopic model. Cancer Res
62:1534-40.
9. Pirocanac E, Nassirpour R, Yang M, Wang J, Nardin S,
Gu J, Fang B, Moossa A, Hoffman R, and Bouvet M (2002) Bax-induction gene therapy of pancreatic cancer. J
Surg Res 106:346.
Impact
of Tumor Formation on Ovarian Cancer Spread
Robert A. Burger, M.D.
University
of California, Irvine
$310,822 / 36 months
New Investigator Award
Ovarian
Cancer
No final report submitted.
John Love, Ph.D.
Alex
B. Burgin, Ph.D.(Previous Principal Investigator)
San
Diego State University
$317,022 / 36 months
New Investigator Award
Ovarian Cancer
No final report submitted.
Targeting
Ceramide to Treat Prostate and Ovarian Cancer
Miles C. Cabot, Ph.D.
John Wayne Cancer Institute
$261,954 / 24 months
Pilot and Feasibility Study Award
Prostate Cancer, Ovarian Cancer
The phenomenon of drug resistance
arising in biological systems is widespread. Increasingly, drug-resistant bacteria and viruses pose a
serious threat to human health.
However, it surprises people to learn that many forms of cancer are also
drug-resistant, and like in other living organisms, this resistance can be
acquired. Resistance to
chemotherapy is the major cause of cancer treatment failure, and prostate and
ovarian cancers represent malignancies in which the development of drug
resistant forms has prevented significant cure with currently available
chemotherapy drugs.
We have pinpointed a gene whose
product is an enzyme that can render chemotherapy ineffective. The enzyme does not destroy the
anticancer drug, per se, but rather accelerates the clearance of a molecule
called ceramide, a lipid that is formed in response to the anticancer
drug. Ceramide acts much like a
chemical messenger and initiates the tumor cell into a death-spiraling cascade.
Our research has demonstrated that
ceramide, generated in cancer cells in response to treatment with natural
product chemotherapy drugs (Adriamycin, Taxol, vinblastine), is rapidly
metabolized by an enzyme called GCS.
This action halts the cytotoxic impact of chemotherapy. The aim of this project is to design
more effective therapies to treat gender-specific, chemotherapy-refractory
cancer. We hypothesize that
blocking cellular ceramide clearance will perpetuate chemotherapy responses. To this end, we have shown that administration
of chemotherapy in conjunction with inhibitors of ceramide metabolism enhances
therapeutic effects. For example,
a regimen consisting of 4-HPR, a vitamin A analog that promotes ceramide
formation, and Tamoxifen, which blocks ceramide clearance, is effective in
killing 90% of prostate cancer cells; whereas, either agent alone is poorly
effective. An exciting aspect of
this approach is that 4-HPR and Tamoxifen are already in clinical use and have
mild side effects.
With regard to ovarian cancer, we
have targeted the gene that produces GCS as opposed to inhibiting GCS directly,
to enhance chemotherapy efficacy.
We have chemically synthesized a short strand of DNA, which is similar
in chemical composition to the DNA in the gene that renders cancer cells “drug
resistant”, except that the sequence of molecules in the strand of DNA has been
scrambled. This strand of
scrambled DNA, termed antisense oligodeoxyribonucleotide (antisense oligo), is
taken up by the cancer cell and used as a template for synthesis; however, the
enzyme that is generated has little function because the blueprint for making
it had been scrambled. This
handicaps the tumor cell making it vulnerable to chemotherapy. Using this approach with drug-resistant
human ovarian cancer cells, we have been able to enhance cellular sensitivity
to Adriamycin by 10-fold. This is
noteworthy because cancer cells often develop resistance to Adriamycin, the
world’s leading chemotherapy drug.
Although this antisense oligo is only a prototype, it can serve as a
model for constructing more powerful reagents to combat chemotherapy
resistance. Work with prostate
cancer cells is planned.
In summary, with both the genetic and the enzyme inhibitor avenues, we have been able to show that targeting ceramide metabolism holds promise as a viable approach to prostate and ovarian cancer treatment. We are working towards expanding this study into the realm of clinical application.
1. Cabot MC
(2002) Ceramide glycosylation and chemotherapy resistance. In Futerman A,
ed., Ceramide Signaling. Landes Bioscience, Georgetown, TX.
2. Wang H, Charles AG, Frankel AJ, and Cabot MC (2003) Increasing intracellular
ceramide: an approach that enhances the cytotoxic response in prostate cancer
cells. Urology 61:1047-52.
3. Senchenkov A, Litvak DA, and Cabot MC (2001) Targeting ceramide metabolism--a
strategy for overcoming drug resistance. J Natl Cancer Inst 93:347-57.
Wenteh Chang, Ph.D.
Stanford
University
$71,820 / 24 months
Postdoctoral Fellowship Award
General Cancer
Triptolide is a diterpenoid
triepoxide purified from a Chinese herb Tripterygium wilfordii. Its immuosuppression and
anti-inflammatory effects proved to be effective in the treatment of leprosy
and rheumatoid arthritis. Recent
studies showed that this drug, in its purified form, is extremely effective to
kill various tumor cell lines. We
have demonstrated the potency of triptolide to kill numerous solid tumor cell
lines in our laboratory, including breast, colon, prostate, and skin cancer
cells when treated alone or in the combinations with other well-known
chemotherapeutic drugs. Moreover,
the potential of triptolide as the anti-tumor agents was demonstrated in nude
mice as the size of grafted tumors was reduced after the administration of
triptolide. To get the insight of
cancer killing by triptolide and explore the possibility to use triptolide as
the cancer drug, we propose to identify and characterize the molecules that are
involved in the killing of tumor cells induced by triptolide.
From previous studies, we showed
that triptolide can cooperate with a variety of chemotherapeutic drugs to
enhance the killing of tumor cells.
One of the well known tumor suppressor, p53, is involved in this effect. We found that the killing of tumor
cells induced by triptolide is associated with the increased levels of p53
protein. In this study, our data
suggest that triptolide can elevate p53 protein synthesis by increasing the
association of p53 message to the protein synthesis machinery. This translational regulation involves
the specific sequence within the 3' untranslated region (UTR), and possibly
some other factors with the ability to associate with this sequence. In a recent study, a 40 kDa protein has
been found by another group to specifically interact with the repression
element within the 3' UTR of p53 RNA.
The modification of a similar molecule by triptolide may be responsible
for the dissociation of its inhibitory effect from the 3' UTR of p53.
The functions of p53 are
well-controlled by the post-translational modification of its protein. At least 18 sites of human p53 proteins
have been shown to be phosphorylated, dephosphorylated, or acetylated following
a variety of stimuli. The active
p53 then induces or inhibits the expression of more than 150 down stream
genes. Among them, p21 mediates
arrest of mammalian cells at the major cell cycle checkpoint. Previously, we demonstrated that the
repression of p21 played a key role to kill tumor cells induced by triptolide,
and this effect could be altered by increasing the levels of p21 proteins in
the tumor cells. Moreover, the
phosphorylation level of p53 proteins was increased after triptolide treatment. To investigate which modification
site(s) of p53 proteins is important to the repression of down stream gene, we
first identify four sites with higher phosphorylation levels after triptolide
treatment. The first mutant p53 is
generated with its serine 15 replaced by an alanine. The response element of p53 derived from the promoter region
of mdm2, another immediate downstream gene of p53, is used to control the
expression of a reporter gene for evaluation. Our data suggest this p53 mutant doesn't have much significant
ability to release the repression effect on gene expression induced by
triptolide. However, we can't
underestimate the possibility that multiple sites, and/or the combinations with
other types of modification, like dephosphorylation and acetylation, may
involve in this gene regulation.
Finally, it is possible that the modified p53 proteins alone are not
sufficient to repress gene expression, but some other targets of triptolide are
required to cooperate with the modified p53 proteins for the death of tumor
cells.
Genhong Cheng, Ph.D.
University
of California, Los Angeles
$319,726 / 36 months
New Investigator Award
Nasopharyngeal Cancer
Epstein-Barr virus (EBV) is a
common human virus, which infects approximately 90% of the adult population
worldwide. It is associated with
various malignancies, including nasopharyngeal carcinoma (NPC), Burkitt’s
lymphoma post-transplantation lymphoproliferative disease, over 60% of
Hodgkin’s lymphomas and non-Hodgkin’s lymphomas related to the acquired
immunodeficiency syndrome (AIDS).
Recent studies indicated that EBV may also be associated with certain
breast cancers, gastric carcinomas and other epithelial cancers. The mechanisms of the disease formation
are not yet well chacterized and no effective approaches are available for
monitoring disease progression and for treating these life-threatening
diseases.
Recent studies have shown that one
EBV viral protein, latent membrane protein 1 (LMP-1), which is essential for
EBV-mediated transformation from normal cells to tumor cells, is able to
increase cellular levels of the epidermal growth factor receptor (EGFR). Interestingly, high levels of EGFR are
causative of over 30% of breast cancers, and drugs inhibiting EGFR have been
used successfully for treating patients with breast cancers. In addition to the upregulation of
EGFR, LMP-1 may also increase the expression levels of Bcl-x, an important
protein involved in cell survival.
Through the grant support, we
found that EGFR is highly overexpressed in tumor cells in over 70% of NPC
samples and approximately 30% of breast cancer tumor samples, suggesting that
EGFR is a likely diagnostic and therapeutic target for both NPC and breast
cancers. In addition, while
Her-2/Neu is expressed more highly in tumor cells than in surrounding normal
cells in approximately 23% of human breast cancer tumor samples, none of the
NPC samples we examined overexpress Her 2/Neu. In addition, we found that many chemotherapy agents commonly
used in clinic, which suppose to kill tumor cells, can actually activate
alternative cell survival pathways (such as the NF-kB-dependent up-regulation
of Bcl-x and Bfl-1 genes) to protect tumor cells. We believe this finding may provide a mechanism for the
development of chemoresistance of cancer cells. Our studies also demonstrated that blocking the
NF-kB-dependent up-regulation of Bcl-x and Bfl-1 genes can greatly reduce
chemoresistance and sensitize chemotherapy-mediated apoptosis. Interestingly, Bcl-x is overexpressed
in most of the NPC and breast cancer tumor samples we examined. Our results suggest that overexpression
of cell growth genes such as EGFR and cell survival genes such as Bcl-x may be
responsible for the development of NPC tumors. We therefore propose a novel strategy to treat NPC tumors by
using combination of NF-kB and EGFR inhibitors.
Siska
I. Corneillie, Ph.D.
University
of California, Riverside
$71,070 / 24 months
Postdoctoral Fellowship Award
General Cancer
P53 is a cellular protein known to be absent or
non-functional in over 50% of all cancers studied to date. The protein is
normally present in low concentrations in the cell. In response to various
stress signals however, the cellular levels of p53 rise and the activated
protein induces the expression of a number of target genes. The overall result
of this process is either cell cycle arrest, or cell death when damage to the
DNA is too severe for repair. In the absence of functional p53, aberrations accumulate
in the cell and ultimately lead to tumor formation and progression.
Surprisingly little however, is known about the basic
mechanism by which p53 activates the transcription of its target genes. The
goal of this project therefore is to better characterize the interaction of p53
with various factors of the general transcription machinery.
Using both transcriptionally active and inactive forms of
p53, we have been able to show that the active, but not the inactive form of
p53, can stimulate the formation of a transcription initiation complex on the
DNA ('TFIID/TFIIA-complex'). Furthermore, only the transcriptionally active
form of p53 can induce the conformational change in this TFIID/TFIIA-complex
required for p53-dependent activation of transcription. Finally, we found that
these interactions require a direct contact between p53 and TFIID.
The importance of this research is related immediately to
the protein under investigation. Since functional p53 is absent in a large
number of cancers, any project intended to address a fundamental aspect of the
mechanism by which this protein functions to prevent cancer, is highly relevant
to our better understanding of the disease. It also may bring us one step
closer to the development of a new or improved treatment for cancer.. Knowledge
about this fundamental interaction mechanism will contribute significantly to
our understanding of p53’s involvement in the prevention of cancer.
1. Xing J, Sheppard HM, Corneillie SI, Liu X. p53
stimulates TFIID-TFIIA-promoter complex assembly, and p53-T antigen complex
inhibits TATA binding protein-TATA interaction. Molecular and Cellular Biology.
2001;21(11):3652-3661.
Hanna Damke, Ph.D.
The
Scripps Research Institute
$369,160 / 36 months
New Investigator Award
General Cancer
Cell death is one of the most
dynamic areas of biological research involving the study of apoptosis and the
role of this phenomenon in development and tissue homeostasis, aging and
disease. Inappropriate apoptosis may cause human diseases like autoimmune
disorders, Alzheimer’s and many forms of cancer. Apoptosis is a highly
organized form of cell death and extensive studies of the complex mechanism of
apoptosis are needed for the understanding and ultimately the control of
apoptosis. Profound implications for medicine from the manipulations of these
processes can be expected, and apoptosis has become a very important target for
therapeutic intervention.
Our research focuses on the GTPase dynamin-2, a protein that naturally occurs in the cell. Previously, dynamin had only been known to be an enzyme that promoted the formation of endocytic membrane invaginations at the plasma membrane which is required for the uptake of nutrien