Education and Training
1979 A Levels, Camden School for Girls, London, UK
1983 B.Sc., University College London, London, UK, Honors in Human Genetics
1990 Ph.D., Royal Post-Graduate Medical School, University of London, London, UK,
Post-Graduate Education and Training
1990-1994 Post-Doctoral Fellowship, Section of Hematology/Oncology, University of Chicago
1994-1996 Research Associate, Section of Hematology/Oncology, University of Chicago
1996-1998 Research Associate - Assistant Professor, Section of Hematology/Oncology, University of Chicago
1998-2005 Lecturer, King’s College School of Medicine, Guy’s Campus, London, UK
1998-2005 Head, Genomic Instability Laboratory, King’s College School of Medicine, Guy’s Campus, London, UK
2005-present Associate Professor, University of Maryland School of Medicine, Baltimore
2015-present Adjunct Associate Professor, VARI’s Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan
Feyruz V. Rassool, PhD, received her doctorate at the Royal Postgraduate Medical School, University of London, UK. She did her postdoctoral training at the University of Chicago and assumed her first independent faculty position studying DNA damage and repair in myeloid malignancies at King’s College London. She has been at the University of Maryland for the last 12 years.
She is an expert in repair of potentially lethal forms of DNA damage, DNA double-strand breaks (DSBs), that play a critical role in generating genomic instability in cancer. Her work has specifically focused on the aberrant expression and activity of these repair pathways in cancer and leukemia cells that not only play a role in genomic instability, but also appear critical for cancer cell survival. These DNA repair components are attractive therapeutic targets. Thus, Dr. Rassool’s work provides a framework for the development and translation of novel therapeutic strategies for patients with leukemia’s and other cancers. Her recent work is focused on targeting DNA repair abnormalities in Cancer and leukemia.
Dr Rassool recently received the Ziskin Award to study the intersection between DNA damage and repair and epigenetic pathways in cancer and she is part of the SU2C stand-up to cancer Epigenetics Dream Team.
Studies to target acute myeloid malignancies and triple negative breast cancers with a combination of DNA repair and epigenetic inhibitors was recently published in Cancer Cell (2016). These studies are the basis for a clinical trial in AML led by Dr Maria Baer, Director of hematologic malignancies at UMGCCC.
DNA damage and repair, genomic instability, targeting DNA repair abnormalities
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 2012:21(3):430-46. doi: 10.1016/j.ccr. 2011.12.029. PMID: 22439938.
Tobin LA, Robert C, Rapoport AP, Gojo I, Baer MR, Tomkinson AE, Rassool FV. Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias. Oncogene 2013:32(14):1784-93. doi: 10.1038/onc.2012.203. PMID: 22641215.
Muvarak N, Kelley S, Robert C, Baer MR, Perrotti D, Gambacorti-Passarini C, Civin C, Scheibner K, Rassool FV. Role of C-MYC in DSB repair in tyrosine kinase activated leukemias. Mol Cancer Res. 2015 Apr;13(4):699-712. doi: 10.1158/1541-7786.MCR-14-0422. Epub 2015 Mar 31. PMID:25828893.
Muvarak N, Chowdhury K, Xia L, Robert C, YongE, Cai Y, Bellani M, Zou Y, Singh ZN, DuongVH, Rutherford T, Nagaria P, Bentzen SM, Seidman MM, Baer MR, Lapidus RG, BaylinSB, Rassool FV. Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents – A Potential Therapy for Cancer, Cancer Cell. 2016 Oct 10;30(4):637-650. doi: 10.1016/j.ccell.2016.09.002.PMID: 27728808.
Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li-Rong Yu, Huili Li, Cynthia A. Zahnow,Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V. Rassool*, Stephen B. Baylin*. CHD4 Acts As An Oncogene With A Driver Role For Initiating And Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes. CANCER-CELL-D-16-00726, accepted for publication.
* denotes co-senior author status.
Rassool FV, Gaymes TJ, Omidvar N, Brady N, Beurlet S, Pla M, Reboul M, Lea N, Chomienne C, Thomas NS, Mufti GJ, Padua RA. Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia? Ca Res 2007:67(18):8762-71. PMID: 17875717.
Sallmyr A, Tomkinson AE, Rassool FV. Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks. Blood 2008:112(4):1413-23. doi: 10.1182/blood-2007-07-104257. PMID: 18524993.
Fan J, Li L, Small D, Rassool F. Cells expressing FLT3/ITD mutations exhibit elevated repair errors generated through alternative NHEJ pathways: implications for genomic instability and therapy. Blood 2010:116(24):5298-305. doi: 10.1182/blood-2010-03-272591. PMID: 20807885.
Li L, Zhang L, Fan J, Greenberg K, Desiderio S, Rassool FV*, Small D*. Defective non-homolo-gous end-joining blocks B-cell development in FLT3/ITD mice. Blood 2011:117(11):3131-9. doi:10.1182/blood-2010-05-286070. PMID: 21228325.
Tobin LA, Robert C, Nagaria P, Chumsri S, Twaddell W, Ioffe OB, Greco GE, Brodie AH, Tomkinson AE, Rassool FV. Targeting abnormal DNA repair in therapy-resistant breast cancers. Mol Cancer Res 2012:10(1):96-107. doi: 10.1158/1541-7786.MCR-11-0255. PMID: 22112941.
Dr Rassool’s work focuses on repair of potentially lethal forms of DNA damage, DNA double strand breaks (DSBs). She reported that an abnormal and highly error-prone version of DSB repair in cancer cells plays a critical role in generating genomic instability. In addition, this abnormal repair pathway appears critical for the survival of leukemia cells but not normal cells, and thus may be an attractive therapeutic target. Importantly, Dr Rassool’s work provides a framework for the development of novel therapeutic strategies in leukemias and other cancers in which abnormal DSB repair is observed.
Both in collaboration and independently, Dr Rassool has extended her work to the development of therapeutic strategies in leukemias and breast cancers that are resistant to standard therapies. One important collaborator in her efforts to target abnormal repair in therapy resistant breast cancer, is the world famous breast cancer researcher at the University of Maryland, Dr Angela Brodie. In their recently published manuscript in Molecular Cancer Research, they demonstrated that hormone therapy-resistant breast cancer cells exhibit significantly increased abnormal repair involving DNA ligase IIIa and poly ADP ribose polymerase (PARP-1), and that these cells are highly sensitive to a combination of PARP and DNA ligase III inhibitors. These results suggest that abnormal DSB repair may serve as biomarkers to identify tumors that are candidates for this therapeutic approach. Importantly, this recently published study was selected to be featured in the "MOLECULAR CANCER RESEARCH Highlights”.
Her work has also involved mechanisms by which embryonic stem cells (ESCs) maintain genomic integrity in response to environmental stress, compared with differentiated cells. Her lab has recently reported that human embryonic stem cells (hESCs) employ at least two strategies to maintain genomic integrity: First, they maintain enhanced levels of DSB repair transcripts and proteins and have high repair efficacy, as evidenced by established NHEJ assays. Second, they are highly sensitive to DNA damage, as evidenced by a high level of apoptosis upon irradiation. Importantly, adult somatic cells, “reprogrammed” to “dedifferentiate” into induced Pluripotent Stem Cells (iPSCs), mimic hESCs in their repair protein expression and repair efficacy, indicating that their DDR pathways are reprogrammed to resemble those of hESCs. In contrast, the differentiated parental cells from which iPSCs are derived have decreased expression of DSB repair components and demonstrate low repair activity and efficacy. Importantly, we have demonstrated that the DNA damage response is an important biomarker for successful reprograming of adult cells into pluripotent stem cells (IPSCs). This work is vital to the future use of IPSCs in regenerative medicine and has resulted in a published manuscript and RO1-equivalent funding from the Maryland Stem Cell Fund.
Most recently, and inspired by the Laura Zisken award in 2012, Dr Rassool has shown that DNA repair and epigenetic pathways interact and that a combination of DNA methyltransferase inhibitors and PARP inhibiotrs work synergistically to trap more PARP, leading to dramatic anti-tumor effects in AML and breast cancers with intact BRCA genes. This work was recently published in Cancer Cell (2016) and has led to a clinical trial in AML funded by the SU2C.
Dr Rassool received the Ziskin Award in 2012 to study the intersection between DNA damage and repair and epigenetic pathways in cancer and she is part of the SU2C stand-up to cancer Epigenetics Dream Team.
07/01/14 - 06/30/18 (Co-Inv., 5%; PI - M. Baer)
“Inhibition of Pim Kinases in Acute Myeloid Leukemia”
VA Merit Review Award
Role: To investigate role of Pim kinase inhibitors in DNA repair in leukemia.
10/01/14 - 09/30/17 (Co-Inv., 10%; PI - S. Baylin (JHU)
“Bringing Epigenetic Therapy to the Management of Ovarian and Other Cancers”
Adelson Foundation (Pilot)
Role: To investigate the role of PARP inhibitors and epigenetic drugs in ovarian cancer.
11/01/14 - 10/30/17 (Co-Inv., 10%); PI - S. Baylin (JHU)
“Clinical Trials for the Combined Use of DNA Demethylating Agents and PARP Inhibitors in Acute Myelogenous Leukemia”
Van Andel-SU2C, Inc.
Role: To investigate the role of PARP inhibitors and epigenetic drugs in ovarian cancer.
07/01/15 - 02/28/17 (PI, 10%)
“Mechanisms for sensitivity to PARP inhibitors in cancer involving ALT NHEJ”
NIH - R21 5R21CA186974-02
10/1/15 - 9/30/18 (PI, 10%)
“DNA Demethylating Agent and PARP Inhibitor Therapy Targeting Aberrant DNA Repair in Acute Myeloid Leukemia (AML)”
Leukemia & Lymphoma Society
11/1/16 - 10/30/17 (Co-Inv., 10%; PI Baer)
“A Phase I/II Multicenter Study Combining Guadecitabine, a DNA Methyltransferase Inhibitor, with Atezolizumab, an Immune Checkpoint Inhibitor, in Patients with Intermediate or High-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia.”
Van Andel-SU2C, Inc.
Role: Provide correlative studies for clinical trial.
07/01/17 - 6/30/19 (PI, 10%)
“Mechanisms for sensitivity to HDAC inhibitors involving PARP trapping in leukemias”
NIH - R21
GRAND RAPIDS, Mich. (March 7, 2017)—A pair of drugs that may be a one-two punch needed to help combat acute myeloid leukemia (AML), an aggressive blood cancer that kills nearly three-fourths of patients within five years of diagnosis, is the focus of a new multi-center clinical trial that will enroll patients at three sites across the U.S.
The trial pairs an investigational PARP inhibitor, talazoparib, with the DNA methyltransferase (DNMT) inhibitor decitabine, which is already approved for the treatment of myelodysplastic syndrome (MDS), a disease that often precedes AML. Preclinical studies show that combining the drugs may maximize their ability to kill cancer cells.
“Long-term survival with AML is quite poor and, unfortunately, our arsenal for treating it has remained largely unchanged for decades,” said Feyruz Rassool, Ph.D., an associate professor of radiation oncology at the University of Maryland School of Medicine, a researcher at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, and a member of the Van Andel Research Institute–Stand Up To Cancer (VARI–SU2C) Epigenetics Dream Team. “Combination therapies, such as talazoparib and decitabine together, allow us to attack cancer from multiple angles at the most basic level for a greater potential effect.”
A paper published last fall in Cancer Cell, which describes the laboratory studies that laid the foundation for the trial, discusses how PARP and DMNT inhibitors enhanced each other when used in combination, rather than individually. Now, the new trial seeks to investigate this promising treatment approach for potential delivery into clinics and hospitals for patients who are suffering from AML.
“The trick with PARP is that it has to arrive at the site of the damage, fix it, and then go away. If it gets trapped there, it kills the cell,” said Stephen Baylin, M.D., co-leader of the VARI–SU2C Epigenetics Dream Team, along with VARI’s Peter Jones, Ph.D., D.Sc., co-head of Cancer Biology at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a Director’s Scholar at VARI. “The same goes for molecules called DNA methyltransferases, which are important for regulating how genetic instructions are read and acted upon. We found that the DNA methyltransferase actually increases the time that PARP gets trapped at the sites of DNA damage, increasing the effectiveness of the PARP inhibitor.”
AML begins as abnormal blood cells in the bone marrow and spreads throughout the circulatory system and beyond, if not diagnosed and treated quickly. Almost 20,000 people in the U.S. are diagnosed with AML every year.
“Acute myeloid leukemia is difficult to treat, especially in older patients and in patients who do not respond to initial treatment or who relapse,” said Maria Baer, M.D., professor of medicine at the University of Maryland School of Medicine, director of Hematologic Malignancies and co-leader of the Experimental Therapeutics Program at the University of Maryland Greenebaum Comprehensive Cancer Center, who is leading the trial. “We hope that this new treatment regimen will help AML patients for whom effective treatments are not currently available.”
The trial is now underway at the University of Maryland Greenebaum Comprehensive Cancer Center in Baltimore and will soon open at Temple University Fox Chase Cancer Center in Philadelphia and University of Southern California in Los Angeles, all affiliated with the VARI–SU2C Epigenetics Dream Team.
The DMNT inhibitor, decitabine, is already FDA-approved to treat MDS and is often used as an off-label chemotherapy for AML. The investigational PARP inhibitor, talazoparib, is being supplied by Medivation, a wholly owned subsidiary of Pfizer, Inc., and is not yet approved by the FDA.
In addition to AML, the combination therapy also has potential to treat other cancers, including those in the breasts and ovaries.
“Our work also shows promise in ovarian cancer and breast cancer—particularly triple-negative breast cancer, which is notoriously difficult to treat,” Rassool said. “If this first clinical trial is successful, we hope to expand our studies to help more patients.”
To date, the VARI–SU2C Epigenetics Dream Team has launched four clinical trials in different cancers, including AML, MDS and metastatic colorectal cancer. Following SU2C’s revolutionary paradigm, the team unites leading investigators and industry partners from around the world to compete against cancer rather than against each other.
Institutional Service – University of Maryland School of Medicine
2006-2011 Reviewer, American Cancer Society (ACS) Institutional Review Grant (IRG), Pilot Project Grants at the University of Maryland Greenebaum Cancer Center (served 1x annually)
2007-present Member, Cancer Biology Curriculum Committee
2008-2013 Organizer, Free Radical Interest Group (FRIG) monthly seminars (year round)
2009-present Member, Graduate Program in Life Science (GPLS) Curriculum Committee
2009-present Member, Master’s Curriculum Committee
2009-2011 Member, School of Medicine Council
2011-2012 Interim Director, Radiobiology Department
2011-present Member, T32 Cancer Biology Steering Committee
2012-present Member, Master’s Program in Translational Research, Core Course
2013-present Member, Translation Laboratory Sciences Advisory Committee
2013-present Reviewer, T32 Grants (1x annually)
2013 Reviewer, Seed Grant Program UMB and UMCP (served 1x)
2014 Reviewer, Dean’s Challenge Grant (served 1x)
2015 Reviewer, Graduate Application for Graduate Program in Toxicology (serve 1x)
2015 Reviewer, Graduate Application for Graduate Program in Biochemistry (serve 1x)
2015-present Member, Funding Submission Peer Review Committee, Radiation Oncology
2005 Moderator, Chromosomes and Cancer: From Translocations to Targeted Therapies, University of Chicago (served 1x)
2006 Chair Person, Baltimore Area Repair Symposium (BARS) – raised $15,000
2008 Moderator, Myelodysplastic Syndromes: Pre-clinical and Translational Science,
Baltimore Area Repair Symposium (BARS) (served 1x)
2008 Chair, DNA Damage and Repair Session, American Society for Therapeutic
Radiology and Oncology (ASTRO) Meeting (served 1x)
2011 Moderator, Clinical Translation of Epigenetic in Cancer Therapy, San Diego, CA
2011-present Reviewer, Nathan Schnaper Summer Intern Program candidates (1x annually)
2012 Co-Organizer and Moderator, 5th Annual Maryland Stem Cell Research
Symposium, Annapolis, MD (served 1x)
2012 Speaker, Stem Cell Center Fund Raiser, Black Olive Inn, Maryland (served 1x)
2013 Moderator, Radiation Oncology Review Course, University of Maryland (served 1x)
2014 Coordinator, American Society of Hematology (ASH) Abstract Review, Category 601: Chromosomal Rearrangements and DNA Repair, San Francisco (served 1x)
2014 Moderator, Category 601: Chromosomal Rearrangements and DNA Repair. American Society of Hematology (ASH), San Francisco (served 1x)
2015 Chair, Minisymposia “Cancer Epigenetics”, American Association of Cancer Research (AACR) Annual Meeting, Philadelphia, PA (serve 1x)
2016 Chair: Special lecture, 18th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy, Houston Texas.
2017 Chair DNA Repair Session. AACR New Frontiers in Cancer Research, Cape Town South Africa January 2017.
2016 Program Committee for the AACR New Frontiers in Cancer Research conference taking place January 18-22, 2017 in Cape Town, South Africa.
2016 AACR regional Advisory Subcommittee on Africa.
2017 AACR-AstraZeneca Fellowship in Ovarian Cancer Research Committee
DNA damage and repair assays
Cell survival assays
Mouse xenograft studies in collaboration with Translational Core Facility UMGCCC.
Lab Equipment: Tissue culture and cell storage: Four C02 incubators, three tissue culture hoods, two 40C refrigerators and two -200C freezers, Coulter cell counter (Z2), liquid nitrogen storage tank; Western blotting analysis: Gel electropheresis equipment (Biorad), including, power supplies (Biorad), Quantitative: End-point PCR machines, real-time PCR machines (Eppendorf), PCR hood, pipettes for PCR; DNA repair assays: bacterial incubator, fume hood, two gel imaging systems, nucleofector (Amaxa); General laboratory equipment: water baths, thermomixers and heat blocks, vortex apparatus, stir plates, hybridization chamber, 40C fridges, two -200C and two -800C freezers, pipetors, six microfuges centrifuges (at 40C and room temperature), three tabletop centrifuges, orbital shakers and rotators (for room temp and cold room reactions), macro- and microbalances, UV-visible spectrophotometer (Nanodrop and Nanovue), dissection, standard, and phase contrast microscopes, a Nikon micropht microscope with Nomarski optics, MJ thermal controller for PCR, fully automated HPLC, ELISA plate reader, cytospin centrifuge for immunofluorescence analysis of suspension cells, sample diluter/dispensers for RIA. Clonogenic Assays: A Synbiosis ProtoCOL3 colony counter. Shared departmental equipment includes standard and ultracentrifuges, a gamma-counter, liquid scintillation counter, microtome, spectrophotometer, cryostat, protein and nucleic acid electrophoresis and blotting system.
Other Shared Equipment:
The Radiation Oncology Research Laboratory is equipped with common equipment necessary for research including a Beckman Optima L-90k ultracentrifuge, a Beckman Avanti J-20XP centrifuge, a Beckman LS-6500 liquid scintillation counter, four large bacterial shakers, incubators for bacterial growth, Sonifier 250 (for ChIP studies), an Alpha-Innotech digital gel acquisition system, phosphoimager, 1 inverted fluorescent microscope, 1 standard Zeiss microscope, and a Zeiss and Nikon phase/brightfield/fluorescence microscope with an MC100 35mm camera, and a CCD digital camera, an X-ray machine, dark room with film processor, and a conference room are on site. In addition, there is joint use equipment located at the University of Maryland, Baltimore including a fluoroimager, dishwashing facilities, electron microscopy, confocal imaging center, mass spectroscopy, flowcytometry, the Center for Fluorescence Spectroscopy, Biopolymer Core Facility for sequencing and DNA Synthesis, and the MCB Freezer Program, an on-site biological reagent storehouse. Machine and electronic shops are available on a time/materials basis.