Scientific Scholar Awardees

Scientific Scholar Recipients
Each year we support multiple Scientific Scholars with $60,000 each for their proposed research. Each award recipient names a mentor who will help guide him or her through the process of becoming an established researcher.

Sarah Beth Gitto, PhD
University of Pennsylvania
Philadelphia, PA, United States

2019 Scientific Scholar Award

Research in Focus: Novel therapies to treat ovarian cancer

Priming the TME with anti-VEGF to enhance the efficacy of dual checkpoint inhibition in PARPi-resistant OC

Recent studies have shown that the use of the PARP inhibitor olaparib increases survival of ovarian cancer. Unfortunately, most patients will become resistant to PARP inhibitors, thus novel treatment strategies are critical for these patients. The presence of immune cells known as tumor-killing T-cells in tumors are associated with better survival in ovarian cancer. Developing therapies that control the surrounding tumor microenvironment and help recruit tumor-killing T-cells to the tumor may be an effective treatment strategy. Additionally, drugs known as immune checkpoint inhibitors have shown promising results in other cancer types, but have not been as effective against ovarian cancer. In this study, Dr. Gitto investigates the modification of the tumor microenvironment to allow tumor-killing T-cells access to the tumor prior to treatment with immune checkpoint inhibitors, to treat PARP inhibitor resistant ovarian cancer.  The physical and chemical barrier surrounding the tumor makes it difficult for tumor-killing T-cells to infiltrate the tumor. The VEGF protein promotes tumor survival through increasing tumor blood supply and stimulating a pro-tumor immune response, preventing tumor-killing T-cells from infiltrating the tumor and killing cancer cells. Dr. Gitto proposes that treating ovarian cancers with a VEGF protein inhibitor, known as Bevacizumab, may reduce the physical and chemical barriers that inhibit T-cells from killing tumor cells. Bevacizumab has been approved for front-line therapy in combination with chemotherapy for ovarian cancer and has shown to have some promising anti-tumor effects when combined with immune checkpoint inhibitors in other cancers. Dr. Gitto will investigate how prior treatment with Bevacizumab may enhance the effectiveness of immune checkpoint inhibitors to treat PARP inhibitor resistant ovarian cancers in a mouse model.

Erin George, MD
University of Pennsylvania
Philadelphia, PA, United States

2019 Lynda’s Fund Scholar Award

Research in Focus: Novel therapies to treat ovarian cancer

Strategies to optimize drug tolerability without compromising efficacy

Most women with ovarian cancer present with advanced stage disease. Large surgeries and toxic chemotherapies are the mainstay of treatment and, despite advances in medicine, most ovarian cancers return. Every tumor is unique in its biology, allowing for the opportunity for tailoring therapy to target these differences. A subset of ovarian cancers, which have high levels of the Cyclin E protein, are especially aggressive. These women’s cancers return quickly, do not respond to standard chemotherapy, and die sooner from their disease. Dr. George and colleagues found that blocking two proteins, WEE1 and ATR, is a promising approach and better than standard chemotherapy to treat these types of tumors. In a preclinical mouse model of this aggressive ovarian cancer, survival was increased more than 3 times compared to standard chemotherapy. Given these findings these drugs are nearly ready for patients in the clinic, however because inhibitors of WEE1 and ATR have overlapping side effects, identifying the optimal dosing strategy is of great importance. Dr. George’s study will help ensure that when this combination goes to clinical trials it is most likely to be well-tolerated and lead to complete and long-lasting responses. Dr. George’s findings have major clinical implications for the treatment of this aggressive and often chemotherapy resistant type of ovarian cancer.

Achuth Padmanabhan, PhD
University of Maryland Baltimore County
Baltimore, MD, United States

2019 Skacel Family Scholar

Research in Focus: Novel therapy to treat ovarian cancer

PROTAC-mediated degradation of oncogenic gain-of-function p53 mutants: A personalized therapeutic strategy for ovarian cancer

Ovarian cancer is the fifth leading cause for cancer-associated deaths among women in the US and is associated with frequent mutations in p53 gene. While some mutations result in the loss of function of the p53 protein, several mutations in the gene result in a mutant protein that gains new functions which promote the growth of the tumor. These gain-of-function p53 mutant proteins help the cancer cells become more aggressive and resistant to chemotherapy. These tumor promoting gain-of-function p53 proteins form very stable aggregates or clusters that accumulate to high levels in cancer cells. Depletion of these mutant p53 proteins in ovarian cancer cells causes the cells to die suggesting that cancer cells need these mutant proteins to survive. Thus, depleting these mutant proteins from cancer cells provides a potential therapeutic opportunity. However, achieving selective depletion of mutant p53 proteins in ovarian cancer cells in a way that can be applied in the clinic has been extremely challenging. In this study, Dr. Padmanabhan proposes to overcome this challenge by developing a novel strategy to selectively deplete gain-of-function mutant p53 proteins in ovarian cancer cells thereby causing cancer cell death. Dr. Padmanabhan will use state of the art chemistry technology to develop Protein Targeting Chimera (PROTAC) to specifically bind mutant p53 to kill ovarian cancer cells implanted in mice. If successful, this project would help pave the way for a personalized and targeted approach for treating ovarian cancer.

Yael Raz Yana, MD
Cedars-Sinai Medical Center
Los Angeles, CA, United States

2019 Cookie Laughlin Scholar Award

Research in Focus: Understanding the biological mechanisms that cause ovarian cancer

Studying the Fallopian Tubes of BRCA Mutation Carriers to Understand the Infrastructure for Malignant Transformation

Though the majority of ovarian cancer patients are postmenopausal, it is unknown how age and postmenopausal conditions contribute to cancer development. Women with inherited BRCA1 gene mutations are at increased risk of ovarian cancer. It is now accepted that most ovarian cancers originate in the fallopian tube. Dr. Raz Yana will study how postmenopausal conditions and status of BRCA mutation alter fallopian tubes to promote ovarian cancer. Fallopian tubes contain several types of cells, including secretory cells and ciliated cells. Dr. Raz Yana and colleagues observed secretory and ciliated cells often form large clusters in fallopian tubes from postmenopausal women. The ratios of secretory and ciliated cells are different in clusters in fallopian tubes of women with BRCA1 mutations compared to women of the same age without BRCA1 mutation. Importantly, secretory cell ‘runs’ have been associated with increased risk of ovarian cancer, suggesting that secretory cell clusters may represent a potential pre-cancer environment. Dr. Raz Yana hypothesizes that fallopian tubes from women with BRCA mutations have earlier and more frequent cell clustering compared to women without BRCA mutation, which in turn creates a more permissive microenvironment for the initiation and progression of cancer. Dr. Raz Yana and colleagues will examine abnormal cell clustering in the fallopian tube tissues of healthy women with BRCA mutations and identify which changes in expression of genes potentially contribute to the formation of the pre-cancer environment. This may lead to the development of new strategies for ovarian cancer prevention and detection.

Kwan Ho Tang, PhD
New York University
New York, NY, United States

2019 Scientific Scholar Award

Research in Focus: Novel therapies to treat ovarian cancer

Targeting SHP2 and MEK in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer is the most lethal gynecological disease. Dr. Tang and colleagues have shown in that a combination treatment of SHP2 inhibitor and MEK inhibitor drugs can effectively target this disease. Importantly, they showed in some cancer models that the combination treatment blocks tumor growth directly and modifies the immune environment of the tumor to make it less favorable for the tumor. In this study, Dr. Tang and colleagues propose detailed investigations of the effect of SHP2/MEK inhibition in novel mouse models of high grade serous ovarian cancer, which have their native, functional immune system. The results of this study would provide a comprehensive understanding of both direct and indirect effects of SHP2/MEK inhibition in high grade serous ovarian cancer, a disease that often demonstrates heavy infiltration of immune cells. This would also allow Dr. Tang and colleagues to design more sophisticated and effective strategies in targeting the disease through combination of immune modulating agents. Given that two different MEK inhibitors are now approved drugs, and two SHP2 inhibitors are currently in Phase I human trials, their results could have immediate relevance for ovarian cancer patients.


Yasuto Kinose, M.D., Ph.D.
University of Pennsylvania
Philadelphia, PA, United States


Project: Evaluation of a novel combination therapy in clear cell ovarian cancer orthotopic patient-derived xenograft models

Research Area: Novel Therapy, Cancer Biology

While clear cell ovarian cancer is a relatively rare subtype of ovarian cancer, it is also the most difficult to treat in advanced stages or when the cancer comes back. It’s been difficult to understand the biology of clear cell ovarian cancer and develop new treatment approaches because there are not enough model systems to study the disease. Dr. Kinose’s work addresses this vital need to identify more effective treatments for this type of ovarian cancer. Clear cell ovarian cancers demonstrate unique genetic mutations that effect the ability of cells to repair their DNA and other functions which are essential for cancer cell survival. Dr. Kinose and his colleagues have discovered a promising new combination using drugs known as WEE1 inhibitors and BET inhibitors that kill these cancer cells when used together. In this project, Dr. Kinose will develop this exciting new combination further by understanding how it works and confirm the findings in novel clear cell ovarian cancer mouse models developed from patient tumors. In these mouse models, pieces of tumors taken from patients can be implanted and grown prior to testing new therapies. The findings from this project may identify a new treatment for this aggressive type of ovarian cancer.

Yaara-oren-rivkin-grantYaara Oren, Ph.D
Broad Institute
Cambridge, MA, United States

Project: Using a novel single-cell lineage tracing technique to uncover the mechanisms driving ovarian cancer recurrence

Research Area: Cancer Biology, Chemotherapy Resistance

Despite a good initial response to chemotherapy, ovarian cancer comes back in the majority of patients and leads to death within 5 years of diagnosis. When the cancer first comes back, it may still be responsive to chemotherapy in many cases before eventually becoming drug resistant. Several mechanisms have been suggested to contribute to the disease coming back but we don’t know exactly how and how much each of these mechanisms impact the process. There is also a need for better experimental models to understand the re-emergence of cancer which are currently lacking, making the development of new therapies that target this crucial stage of the disease difficult. Dr. Oren proposes to uncover and understand the factors that contribute to the re-emergence of ovarian cancer that is still responsive to chemotherapy, by using a new method that allows her to trace how individual single cells respond to multiple rounds of chemotherapy. Her novel tracing technique will allow her to study how an ovarian cancer cell’s past behavior and pedigree affect its ability to survive drug treatment. Dr. Oren will combine several techniques including microscopy, sequencing, mathematical modeling and patient data to expose not only what makes cells resistant to initial treatment but also what effects their ability to regenerate the tumor. This unique methodology will allow Dr. Oren to identify which genes and cellular pathways are important for relapse. The insights gained from this integrated approach will help devise new drug therapies that delay or even prevent the emergence of resistant ovarian cancer.

alice-lee-rivkin-grantAlice Wen-Ron Lee, Ph.D.
California State University Fullerton
Fullerton, CA, United States

Project: Exploring the impact of infertility and its treatments on risk of ovarian cancer

Research Area: Prevention, Cancer Biology

Some studies have previously indicated that there may be a relationship between infertility and ovarian cancer risk, but this connection is very poorly understood. Infertility is a significant public health problem in the United States and an increasing percentage of women have experienced infertility issues over the last decade. Women who have never given birth are at an increased risk of ovarian cancer. This group includes both infertile women who cannot have a baby as well as fertile women who choose not to have a baby. In addition, drugs used to treat infertility and the underlying causes of infertility may pose different risks for ovarian cancer. Teasing apart these effects has been a challenge given that the previously conducted studies were done with small numbers of patients and limited infertility information. Dr. Lee proposes to clarify infertility’s relationship with the risk of ovarian cancer by doing the largest analysis of comprehensive infertility data to date, using 14 epidemiologic studies participating in the Ovarian Cancer Association Consortium (OCAC). The findings from this study will help us better understand the significance of infertility and infertility treatment for ovarian cancer risk.

Kaitlin Fogg, PhD
Kaitlin Fogg, PhD
University of Wisconsin

The Influence of Macrophages on the Expansion of Ovarian Cancer Metastases

Ovarian tumors metastasize or spread by cells detaching from the primary tumor and implanting on nearby organs such as the omentum, an apron-like membrane that insulates the abdominal organs. The factors that lead to the metastases of ovarian tumors are still largely unknown. However, immune cells called macrophages multiply in the fluid around the abdominal cavity as the cancer progresses. Dr. Fogg will investigate how these immune cells promote tumor metastasis and subsequent thickening of the omentum. Using a combination of ovarian cancer cells, macrophages, and abdominal tissue, Dr. Fogg will construct a much needed 3-D model mimicking the environment of the abdominal cavity in a woman with ovarian cancer before metastasis. She will use a statistical model to determine how the macrophages stimulate the tumor cells to start spreading and then change the surrounding tissue to accommodate the implanting tumor. These findings will provide a window into how ovarian cancer spreads and may help identify new treatment strategies to prevent or delay the process.

Elizabeth Harmon Stover, MD, PhD
Elizabeth Harmon Stover, MD, PhD
Dana-Farber Cancer Institute

Genomic analysis of plasma cell-free tumor DNA to evaluate clinical mechanisms of drug resistance in ovarian cancer

Many ovarian cancers are able to resist drug treatment and therefore recur after months or years, posing a major challenge for clinicians and researchers. Currently research of resistant tumors is limited because biopsies are rarely collected from patients with recurrent ovarian cancer, making it difficult to study changes in the DNA that may cause resistance. Dr. Stover will use new technology to extract tumor DNA that is circulating in the patient from blood samples. By studying the DNA from new tumors and comparing it to DNA from recurring cancers, Dr. Stover will be able to find mutations that differ between the two, leading to important understanding of how the tumor is able to return. Furthermore, this technique will allow Dr. Stover to observe how mutations change over time in the same patient, potentially altering to confer drug resistance.  Overall, this work will lead to the discovery of mechanisms by which ovarian cancers become resistant to treatment, a key step to finding essential new therapies to overcome resistance.

Erin George, MD
University of Pennsylvania
2016 Skacel Family Scholar

Targeting the ATR/CHK1 pathway in high grade serous ovarian cancer with ATR inhibitors

New treatments are needed for recurrent ovarian cancer, a subset of which is more aggressive than the original cancer and has no effective treatment. Aggressive recurrent cancers rely on DNA repair pathways, involving proteins called ATR and CHK1, to repair damage to DNA caused by chemotherapy. Dr. George will target this pathway with a novel ATR inhibitor to stop cell growth and tumor formation, using new ovarian cancer models derived from patients’ recurrent tumors. These findings may have major clinical implications for the treatment of this aggressive and often chemotherapy resistant type of ovarian cancer.

Melissa Merritt, PhD
Imperial College London

Obesity-related factors and ovarian cancer survival

Women diagnosed with ovarian cancer have a poor prognosis, and there are currently no recommendations for lifestyle modifications that may influence survival after a diagnosis. Dr. Merritt will evaluate whether obesity-related factors, including Body Mass Index (BMI), waist circumference, physical activity, and adherence to healthy lifestyle recommendations, influences ovarian cancer survival. The long-term goal of this study is to identify whether pre-diagnostic obesity-related factors may influence survival among women with ovarian cancer. If so, clinical recommendations could be developed so that patients may be able to improve their health and prognosis following an ovarian cancer diagnosis.

David Pepin, PhD
Massachusetts General Hospital

AAV9 gene therapy using a novel engineered MIS to treat ovarian cancer

Ovarian cancer tumors are made up mostly of cells that respond well to chemotherapy, but a minority of stem-like cells survive treatment and ultimately lead to chemoresistant recurrence. However, this type of cancer stem cell is inhibited by Mullerian Inhibiting Substance (MIS). Dr. Pepin is evaluating a modified version of MIS, which has been engineered to have greater potency, as well as an alternative delivery mechanism using viral gene therapy, in preclinical trials. The goal of the study is to develop gene therapy as a supplement to the current standard of care and would offer permanent protection from chemoresistant recurrences after initial surgery and chemotherapy.

Remi Buisson, PhD
Massachusetts General Hospital

Unraveling the role of ATR in DNA repair and ovarian cancer therapy

Proteins involved in the surveillance of genomic integrity, including BRCA1, BRCA2, and PALB2, help detect damage to DNA in cells and ensure that repairs are made when needed. Cells with mutations in BRCA1, BRCA2, and PALB2 have been associated with a heightened lifetime risk for ovarian cancer development and are extremely sensitive to inhibitors of the DNA repair protein PARP. These PARP inhibitors have recently emerged as promising anti-cancer drugs. However, mutations in BRCA genes and PALB2 account only for 15-20% of ovarian cancer. Dr. Buisson’s project will hone in on inhibitors of ATR kinase, a key protein regulating DNA damage signaling and DNA repair, as a way of rendering the other 80-85% of ovarian cancers sensitive to PARP inhibitors and other chemotherapeutics.

Mark Eckert, PhD
University of Chicago

Targeting T-LAK cell-originated protein kinase (TOPK) for ovarian cancer therapy

Ovarian cancer is one of the most lethal cancers due to a lack of effective therapies. Dr. Eckert’s lab recently found that the protein T-LAK cell-originated protein kinase (TOPK) is expressed in ovarian cancer cells, but not most normal tissues. TOPK has roles in multiple cellular processes including DNA damage response, cell division, and metastasis. Excitingly, a small molecule inhibitor of TOPK was recently developed that has minimal toxicity to normal cells but effectively kills TOPK-expressing ovarian cancer cells, including cells from ovarian cancer patients. Dr. Eckert’s project will investigate the biological roles of TOPK in regulating ovarian cancer progression and directly test the efficacy and safety of TOPK inhibitors in patient samples and models of ovarian cancer.

Benjamin Izar, MD, PhD
Dana-Farber Cancer Institute

Single-cell transcriptome analysis of treatment-resistant ovarian cancer and new strategies for drug discovery

Dr. Izar will be studying in fine detail the molecular changes that take place from the time that ovarian cancer cells respond to platinum chemotherapy to when they become resistant. He will employ an innovative genetic testing method to study ovarian cancer cells found in ascites (abdominal fluid) from ovarian cancer patients. This method takes single cells sloughed off from a tumor into ascites to evaluate all of the genes that are active at the moment that cancer cells become resistant. Looking at individual cells will allow Dr. Izar to see in great detail certain tumor sub-populations, including cancer stem cells, which are responsible for resistance over time. By understanding the mechanisms of treatment failure (resistance) that are invisible to other approaches, he will be able to generate new targets for therapy.

Elizabeth Poole, PhD
Brigham and Women’s Hospital
2015 Skacel Family Scholar

Medication use and ovarian cancer survival

Although factors that contribute to ovarian cancer risk prior to diagnosis are currently being teased apart, factors which contribute to survival after a diagnosis of ovarian cancer have not yet been well studied. Dr. Poole’s project will develop the Nurses’ Health Study (two large prospective studies with over 30 years of follow up) to study factors that contribute to ovarian cancer survival including use of anti-inflammatory medications (e.g. aspirin and other non-steroidal anti-inflammatory drugs) and anti-stress medications (e.g. anti-depressants, beta blockers, anti-anxiety medications). Importantly, Dr. Poole has access to and will analyze information from women both before and after diagnosis, making this a unique project for identifying changes that women can make to their lifestyle to improve their survival.

Alexandra Snyder Charen, MD
Sloan-Kettering Institute for Cancer Researchr

Chemotherapy, Somatic Mutations, and Neoantigens in Ovarian Cancer

Immunotherapy is a new treatment that boosts a patient’s immune system to attack ovarian cancer cells. Dr. Synder Charen’s lab has already shown in melanoma that when a tumor has a large number of genetic abnormalities (mutations), the immune system can better “see” and attack the tumor cells. Ovarian cancer cells do not have as many mutations as melanoma cells, but undergoing chemotherapy can cause additional mutations in cancer cells. This study will address whether chemotherapy can cause changes in ovarian cancer cells that allow the immune system the ability to see and potentially attack the tumors. These results will guide future strategies for giving immunotherapy in more effective ways.

Michael Goldberg, PhD
Dana-Farber Cancer Institute
2014 Kirwin-Hinton Family Scholar

Unraveling the role of ATR in DNA repair and ovarian cancer therapy

The majority of cancer therapies attempt to kill tumor cells using drugs that are often toxic. Many patients relapse because residual cells can establish new drug-resistant tumors. Unlike traditional therapies, the immune system can adapt to the evolving tumor. In fact, immune cell infiltration into tumors is the best known predictor of patient outcomes. Frustratingly, tumors secrete a physical barrier to prevent the penetration of immune cells and other medicines. Accordingly, Dr. Goldberg is developing nanoparticles that break down this obstruction (like a molecular battering ram through a fortress wall) to facilitate immune cell and drug penetration, thereby improving survival outcomes.

Pradeep Raghavan, PhD
University of Texas MD Anderson Cancer Center

Unraveling the oncogenic effects of amplified miRNAs in High Grade Serous Epithelial Ovarian Cancer

Cancer cells are abnormal partly by having increased copies of certain genes (DNA copy number aberrations), which is an important hallmark of high-grade serous ovarian cancer. Non-protein coding genes such as microRNAs have recently been implicated in both tumor initiation and progression and represent understudied potential drivers of cancer behavior. Dr. Raghavan‘s preliminary data shows that microRNA miR551b is amplified in approximately 35% of ovarian cancer patients. Initial evidence suggests that miR551b operates by hijacking the tumor suppressor pathways which block the growth and development of cancer. In this project, he will identify the mechanisms underlying how miR551b promotes tumor growth and metastasis as well as therapeutic opportunities.

Capucine Van Rechem, PhD
Massachusetts General Hospital
2014 Skacel Family Scholar

Copy Gain and Resistance: Uncovering Roles for Epigenetic Regulation in Ovarian Cancer

A major issue in the treatment of ovarian cancer is the development of resistance to standard chemotherapy. Such drug resistance has been linked to the gain of a specific genomic region, 1q12-1q21. Dr. Van Rechem recently demonstrated that the amplification of a regulator of genome organization, KDM4A, is associated with a faster time to death in ovarian cancer patients and also caused 1q21 gain. Therefore, the project will investigate the function of KDM4A in promoting drug resistance in ovarian cancer. These studies will bridge molecular mechanisms and clinical relationships so that disease mechanisms and possible treatment options for ovarian cancer patients can be identified.

Photo: Bo Jungmayer
Jessica Bertout, PhD, VMD
Fred Hutchinson Cancer Research Center
2013 Gilman Family Scholar

High-Resolution Detection of Somatic Ovarian Cancer Mutations in Bodily Fluids

Owing to a lack of effective screening tests, 80% of ovarian cancer patients are diagnosed in late stages of the disease at which point there are low survival rates. Methods that enumerate tumor cells and tumor DNA circulating in bodily fluids are currently under intense investigation for early detection and cancer diagnostics; however, no existing technology meets the high sensitivity and specificity requirements needed to attain these goals. Dr. Bertout proposes to use new technologies, building upon Next Generation Sequencing technologies to enable exquisitely sensitive cancer-specific mutation detection, to overcome these challenges, to permit the noninvasive early detection of ovarian cancer, and to extend patient survival.

John Paul Shen, MD
University of California, San Diego

Improving Outcomes in Ovarian Cancer: A Network Genomics Approach

Technological advances now allow for sequencing of tumors from large patient cohorts. However, this knowledge of the cancer genome has not yet been translated into the clinical practice of oncology. Dr. Shen works in the Ideker lab which has developed a novel bioinformatic technique called network-based stratification that incorporates knowledge of genetic networks with somatic mutation profiles to allow for the unsupervised clustering of tumors into clinically relevant subtypes. This technique has demonstrated promise in predicting patient prognosis and response to platinum chemotherapy. Dr. Shen proposes validation of this method in vitro, the development of a clinical biomarker based on these subtypes, and a pilot test of said biomarker on primary tumor samples.

Barbara Norquist, MD
University of Washington
2013 Skacel Family Scholar

Genes Contributing to Hereditary Ovarian Cancer in BRCA1/2 Wildtype Families

Nearly a quarter of ovarian cancer cases may be caused by inherited mutations, with a significant portion caused by mutations in genes other than BRCA1 and BRCA2 (BRCA1/2). Next generation sequencing techniques have made it possible to test for mutations in multiple genes simultaneously. However, little is known about the risks of carrying non-BRCA1/2 mutations, making it challenging to counsel healthy patients found to have mutations. Dr. Norquist plans to test for non-BRCA1/2 mutations in new and existing families with hereditary ovarian cancer in order to better define the risks of carrying these mutations and optimize strategies for prevention of cancer.

Christina Gewinner, PhD
University College London Cancer Institute
2012 Skacel Family Scholar

Identification of novel drug targets for INPP4B-deficient ovarian tumours

Dr. Gewinner’s lab has previously identified a gene called inositol polyphosphate 4-phosphatase type II (INPP4B) which no longer functions in approximately 40% of ovarian tumors. Patients with such tumors have poor survival rates. She has demonstrated that INPP4B deficiency is similar to BRCA1/2 mutations in that DNA repair is defective in cells which harbor these deficiencies. Recently in clinical trials, inhibitors that target DNA repair enzymes have been used to treat ovarian cancer patients with BRCA1/2 mutations. These inhibitors are effective at forcing tumor cells to undergo cell death. Because of the similarity of INPP4B deficiency to BRCA1/2, Dr. Gewinner hypothesizes that INPP4B-deficient ovarian tumors may also respond to inhibitor treatment and that INPP4B can be used as a predictive diagnostic biomarker.

Brigitte Thériault, PhD
Ontario Cancer Institute

Modulation of KIF14 overexpression in ovarian cancer

Dr. Thériault’s lab had previously discovered that the gene KIF14 is present in high amounts in the majority of ovarian cancers, and that patients with high KIF14 have much worse survival than patients with low KIF14. KIF14 is normally found in cells that are growing and dividing and is usually not found in adult human tissues. Her prior research in cell cultures and in animal models has shown that accumulation of KIF14 leads to tumor spread and blocking KIF14 causes tumor cell death. Dr. Thériault’s goal in this project is to understand how tumors accumulate such high amounts of KIF14 so that she can find ways to block KIF14 production, stop tumor cell growth, and improve the survival of ovarian cancer patients.

Anne Noonan, MB BCh BAO, MSc, MRCPI
National Cancer Institute
2012 Gilman Family Scholar

Proteomic biomarker development for optimal sequencing of doxetaxel & SMACmimetic

The drug TL32711 can stimulate ovarian cancer cell death by decreasing proteins that inhibit cell death and decreasing signaling through the NFkB signalling pathway that is known to be overactive in ovarian cancer. This cascade of protein changes could work with a traditional chemotherapy agent called docetaxel to increase ovarian cancer cell death. Dr. Noonan will focus on an enzyme called caspase-8 which is an important link between NFkB and cell death pathways to see if she can tip the balance toward cell death in ovarian cancer tumors. The aim of Dr. Noonan’s project is to determine how best to combine TL32711 and docetaxel and to discover if protein biomarkers can aid the selection of patients for this drug combination in future clinical trials.

John Liao, MD, PhD
University of Washington
2011 Gilman Family Scholar

Development of a Polyepitope DNA Vaccine for Ovarian Cancer Immunotherapy

While ovarian cancer patients can respond to chemotherapy and achieve remission, the majority of advanced stage patients succumb to recurrent disease. Strategies harnessing the immune system have the potential to augment available therapies, prolong remissions, and prevent relapses. Vaccines generating immune responses against proteins in ovarian cancer cells could offer a possibility of selectively killing those cells. Dr. Liao has identified 6 proteins associated with poor prognosis. Vaccines targeting fragments of these 6 proteins will then be tested in a mouse model for ovarian cancer to evaluate safety and effectiveness in preparation for clinical trials.

Fiona Simpkins, MD
University of Miami

Characterization of Subpopulations Capable of Self-Renewal in Ovarian Cancers

Most ovarian cancer patients suffer disease recurrence, and most available chemotherapies are toxic and stop working. Cancer stem cells comprise a subpopulation of cells capable of self-renewal and are resistant to chemotherapy. By characterizing such subpopulations and determining which signaling pathways drive their growth, Dr. Simpkins would like to develop better strategies to target these subpopulations and overcome drug resistance. This project will characterize the self-renewal potential of cell populations expressing different surface markers suggestive of “stemness” in ovarian cancer, determine developmental and mitogenic signaling pathways unique to these populations, and determine how targeted treatments effect these subpopulations.

Young Min Chung, PhD
Stanford University School of Medicine

Targeting Ovarian Cancer with Combination of Olaparib and Trifluoperazine

Dr. Chung is developing innovative therapeutic strategies by combining a clinically used small-molecule drug called trifluoperazine (TFP) and a chemical compound named Olaparib, which is an inhibitor of an enzyme called PARP, to suppress advanced ovarian cancer and to overcome PARP inhibitor-unresponsive ovarian cancer. In addition, novel biomarkers will be identified for monitoring therapeutic sensitivities in ovarian cancer. Ultimately, the results of this project will be used to design a clinical trial to treat patients with advanced ovarian cancer.

Ramandeep Rattan, PhD
Mayo Clinic

TCEAL7, a novel regulator of NFkB-IL-6/STAT3 pathway in ovarian cancer

The causes of ovarian cancer are not well understood because of the complexity and the lack of understanding of the various genetic alterations in the development of ovarian cancer and its progression to chemoresistant disease. Dr. Rattan’s study is poised to be the very first report of a novel tumor suppressor gene TCEAL7, with the ability to transform nonmalignant ovarian surface epithelial cells to a malignant state by modulating the signaling of oncogenic transcription factors like NFκB and STAT3. Dr. Rattan’s goal is to provide valuable information towards identification of a novel gene and signaling pathways that lead to the development of ovarian cancer, which can be further exploited in developing new detection methods and designing therapeutic management for ovarian cancer. Most importantly, the resources generated from this study will be available to other investigators interested in advancing the understanding of ovarian cancer pathology in the hope that these advances will soon benefit ovarian cancer patients.

Melissa Thrall, MD
University of Washington

A population based evaluation of the use and outcomes of neoadjuvant chemotherapy

The current standard of care for the treatment of advanced stage ovarian cancer involves surgery with a maximal effort to remove all visible tumor followed by the administration of platinum based chemotherapy. However not all women with advanced ovarian cancer are treated according to clinical guidelines, and delay in surgery for the administration of chemotherapy may result in worse outcomes. Dr. Thrall’s study aims to evaluate factors associated with this variation in care and how this impacts the outcomes of women with advanced ovarian cancer in a large population based sample of patient treated in the last 10 years.

Melissa Thompson, PhD
University of Texas MD Anderson Cancer Center

The Role of the Tumor Microenvironment in Ovarian Cancer Progression

Ovarian cancer is the deadliest gynecological cancer, accounting for 15,520 deaths annually. Preliminary studies by Dr. Thompson indicate that the tumor microenvironment enables and promotes tumor progression and chemoresistance, possibly through the expression of SFRP2. With this study, Dr. Thompson will demonstrate the specific mechanisms by which the microenvironment promotes ovarian cancer development and progression, specifically overexpression of SFRP2 using gene expression methods, purified protein, and primary cells in conventional 2D and newly developed 3D models. Furthermore, she will characterize the molecular mechanisms that allow for cancer progression, leading to increased understanding of ovarian cancer and possibly better diagnostic and/or treatment methods.

Masafumi Toyoshima, MD, PhD
Fred Hutchinson Cancer Research Center

Identification of Targeted Therapies for MYC-Amplified Ovarian Cancer By Functional Genomics

The main goal of Dr. Toyoshima’s research is to investigate whether MYC synthetic lethal genes can be therapeutic targets for ovarian cancer in women whose MYC gene is amplified. Using a siRNA screening strategy this study will look to uncover genes that are essential for the survival of ovarian cancers with alteration of c-MYC expression. Specifically, Dr. Toyoshima will use siRNA and lentiviral vectors expressing short hairpin (sh)RNAs for stable knockdown of a selected group of MYC-synthetic lethal genes, and utilize available small molecule compounds to inhibit the function of these genes. These genes could represent great drug targets for ovarian cancer treatment.

Amelie Margarete Lutz, MD, PhD
Stanford University
2009 Gilman Family Scholar

Early Detection of Ovarian Cancer Using Targeted Microbubble-Enhanced Ultrasound

The primary objective of Dr. Lutz’s proposal is to validate and refine molecularly targeted microbubble contrast enhanced ultrasound (CEUS) for non-invasive, in-vivo imaging of the ovarian cancer-related angiogenesis. Like other solid tumors, ovarian cancer is critically dependent on functional vascular supply for tumor growth and metastasis. Angiogenesis, the recruitment of new blood vessels, occurs at a very early stage in ovarian cancer development. This work addresses an ovarian-specific target associated with angiogenesis. The translational goal is to apply the approach as part of a multi-modal ovarian cancer screening strategy.

Elda Righi, MD
DFCI/Harvard Cancer Center, Massachusettes General Hospital (East)

Blockade of the CXCL12 and VEGF axes in ovarian cancer

One of the reasons ovarian cancer progresses with few evident symptoms may be the combination of ways in which the cancer escapes the patient’s immune system and organizes a vascular supply to serve its own needs. CXCL12 and VEGF are two factors made in excess by human ovarian cancer and they appear to work together to increase each others effects adding to the ways in which the tumor escapes from control. Dr. Righi, through excellent collaborators to mouse models, proposes to test the idea that blockade of both CXCL12 and VEGF would be significantly better than blocking either one. If successful, this work would add a new dimension to therapy for ovarian cancer patients.

Shailendra Giri, PhD
Mayo Clinic

S-nitrosylation mediated inactiviation of TSG in ovarian cancer

Chronic inflammation has become a well-accepted risk factor for epithelial-derived malignancies, including ovarian cancer. But how inflammation contributes to the process of carcinogenesis is a grey area. If successful, Dr. Giri’s study will elucidate the possible novel regulation of chemical inactivation of LKB1-AMPK pathway by inflammatory mediators in ovarian cancer and lead to a better understanding of the inflammation mediated mechanisms and open up new therapeutic approaches to control inflammation which is an under investigated area of ovarian cancer.

Christina Annunziata, MD, PhD
National Cancer Institute

Characterization of NF-kB signaling as a therapeutic target in ovarian cancer

The NF-kB family of transcription factors has been implicated in the increase of ovarian cancer cell lines, but the significance and the mechanism of signaling is unknown. Initial experiments identified a subset of ovarian cancer cell lines that are dependent on NF-kB signaling for growth and survival. Dr. Annunziata, with the guidance of her mentor, Dr. Elise Kohn, will investigate the hypothesis that constitutive NF-kB signaling defines a subset of ovarian cancer susceptible to therapeutic targeting of this pathway.

Keren Levanon, MD, PhD
Dana-Farber Cancer Institute

The Fallopian Tube as field of origin of ovarian serous carcinoma

Research on ovarian carcinogenesis has traditionally focused on the ovarian surface epithelium as the fields of origin. More recently, the secretory cell of the fallopian tube has emerged as an alternate cell-of-origin for ovarian and pelvic serous carcinomas, the most aggressive subtype of the disease. Under the direction of mentors Dr. Ron Drapkin and Dr. Christopher Crum, the ultimate goal of this project is to elucidate the fundamental processes that lead to ovarian serous tumorigenesis.

Jean-Bernard Lazaro, PhD
Dana-Farber Cancer Institute

Targeting DNA repair genes and the nucleolar proteome to increase cisplatin sensitivity in ovarian cancer

Patients with ovarian cancer who are treated with cisplatin often develop resistance to the drug, as cisplatin acts by damaging cellular DNA, which in turn induces apoptosis. Repair of cisplatin-induced DNA damage by a few cancer cells may cause recurrence of a chemo-resistant cancer. It is likely that controlling the mechanism leading to cisplatin resistance would greatly enhance the efficiency of cisplatin therapy. Dr. Lazaro will work with his mentor, Dr. J. Dirk Iglehart, to define molecular targets to improve cisplatin sensitivity.

Jason Wilken, PhD, BS
Yale University

Overcoming Primary Herceptin Resistance in Ovarian Cancer

Herceptin, a therapeutic antibody that targets ErbB2 and has a well-tolerated safety profile has proven exceptionally useful as a treatment for ErbB2+ breast cancer patients. Surprisingly, Herceptin has proven to be ineffective as a treatment option for ovarian cancer. Dr. Wilken, with the guidance of his mentors Dr. Andre Baron and Dr. Nita Maihle, will study why ovarian tumors and cells exhibit primary resistance to Herceptin treatment and test the hypothesis that primary Herceptin resistant ovarian cancers become predictably susceptible to alternate ErbB-targeted therapies, based on Herceptin-induced changes in ErbB receptor expression.

Mary Zhang, PhD
University of South Florida

Role of HDAC6 and its novel substrate cortactin in ovarian cancer cell motility

HDACs are a group of enzymes that regulate cell growth and migration, and hence are likely involved with the metastases of ovarian cancer. This study will examine the role between these enzymes and the molecular events of cancer spread and growth, which could lead to more effective therapy.

Melissa Fishel, PhD
Indiana University School of Medicine

Enhancement of ovarian cancer to chemotherapeutics agents, cisplatin and TMZ, using small molecules, BG and MX

With the exception of a small percentage of patients presenting with stage IA/IB ovarian cancer, surgery along is inadequate treatment. However, virtually all patients who die from ovarian cancer have intrinsic or acquired platinum-resistant disease. Our overall goal is to improve upon current, and discover novel, chemotherapeutic agent therapy for ovarian cancer. To accomplish this, this study will investigate the modulation of two prominent DNA damaging agents: cisplatin and TMZ. Combination therapy has potential for first-line therapy and/or as second-line therapy for patients who have failed standard platinum plus paclitaxel chemotherapy. The applicability of the TMZ+MX treatment lies in the fact that the therapeutic target, i.e. DNA repair, is expressed in all ovarian cancers, thus circumventing the problem of differential expression by tumor cell subpopulations.

Rosemary Foster, PhD
Massachusetts General Hospital

Identification and Characterization of the Ovarian Cancer Stem Cell

Cancer stem cells have recently been identified in some solid tumors and are thought to drive tumor formation. Most tumors likely contain rare subpopulations of stem-like cells that would serve as critical targets of more clinically effective therapies. Our research experiments are designed to provide both convincing evidence of the existence of the ovarian cancer stem cell and initial characterization of the stem cell population. The isolation and characterization of a purified ovarian cancer stem cell population will provide new information about fundamental ovarian cancer biology leading to identification of specific therapeutic targets and development of more intelligent treatment strategies.