Medical Student Research Fellowship for Summer 2009
Mentor: Elisabeth D. Martinez, Ph.D.
Department: Pharmacology/Hamon Center for Therapeutic Oncology Research
Room number: NB8.218A (office) NB8.114 (lab)
Mail Code: 8593
Phone number: 214-648-5150
Project title: Epigenetic enzymes as therapeutic targets and prognostic markers in breast cancer
Human subjects IRB approved project number (where applicable): IRB exemption, IRB#122008-052
Animal subjects IRB approved project number (where applicable): N/A
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Patient-based research (patient samples)
Brief Description of Project:
It has been estimated that epigenetic changes are at least ten to forty times more frequent in cancers, including breast cancer, than genetic mutations. Epigenetic enzymes are therefore potential targets for cancer-specific deregulation at all stages of the oncogenic process. Currently, there is no information available on the expression of the epigenetic enzyme family in normal vs. cancer breast epithelia or across breast cancer stages or subtypes except for very limited data based on micro-array expression measures for a few enzymes. We propose to profile the expression of the entire family of epigenetic enzymes (consisting of over 50 members) in breast cancer patient samples and to define correlations between this expression and breast cancer stage or subtype. We envision that this study will enable us to define groups of enzymes as novel molecular targets for epigenetic therapy and as diagnostic or prognostic markers to guide the classification and treatment of disease subtypes for breast malignancies. This would be a completely novel finding of broad impact that can open up an entirely new line of investigation for future breast cancer therapeutic development and diagnostic applications. Using this approach, we are particularly excited about the possibility of defining clinically relevant 'epigenetic subgroups' and new molecular targets within the heterogeneous "triple negative" breast cancers which do not respond to hormone therapy nor to Her2 targeted therapy.
Our objectives for this project are to profile the expression of all known human epigenetic enzymes in over 150 patient breast cancer samples by high throughput quantitative RT-PCR with the aims of:
1) Identifying subsets of epigenetic enzymes as novel therapeutic targets and/or as biomarkers across breast cancer stages/histological types and;
2) Evaluating whether the expression of epigenetic enzymes has diagnostic or prognostic value for breast cancer.
These aims will allow us to identify subsets of epigenetic enzymes potentially involved in breast cancer development, progression and metastasis that may constitute novel 'drugable' targets and biomarkers.
The project is being carried out as part of a NCT Pilot award. The student will take the lead in processing samples, doing the RT-PCR experiments and in basic data analysis. Primer design and validation, sample selection and in-depth statistical analysis will be done in collaboration with experts already on the project.
Previous Research Activities or Publications with Medical Students:
" Duri Yun (medical student at University of Illionois, Chicago): summer
intern (2002), NCI, NIH
" Badri Modi (medical student at Yale School of Medicine): summer intern (2006), UTSW
Poster presentations were made by these students.