2015 Outside the Box Recipients
Laureen Ojalvo, MD, PhD is a gynecologic oncology fellow on The Kelly Gynecologic Oncology Service at Johns Hopkins Hospital. She works under the mentorship of Leisha Emens, MD, PhD whose laboratory focuses on a better understanding of the immune microenvironment in cancer and novel ways in which to target it. Dr. Emens is the principle investigator on multiple immunotherapy clinical trials including those involving cancer vaccines and immune checkpoint molecule inhibitors and continues to use the clinic to inform laboratory research, and vice versa. Dr. Ojalvo has a longstanding interest in tumor associated macrophages (TAMs) and how these innate immune cells affect a cancer’s microenvironment and overall disease progression. Clinically, a high density of TAMs correlates with worse cancer prognosis in multiple cancers, including ovarian. TAMs are implicated in multiple processes to promote tumor progression, and recently shown to express checkpoint inhibitor molecules – molecules that attenuate an activated immune response to prevent tumor clearance by the adaptive immune system. Dr. Ojalvo’s proposed research will evaluate patterns of TAMs and checkpoint molecules in human ovarian cancer to better understand how TAMs contribute to the immune suppressed tumor microenvironment. Moreover, this work aims to inform clinical trials of checkpoint inhibitors in ovarian cancer to better understand how they work in this disease and how TAMs may be mediating their efficacy. We are thrilled to have awarded Dr. Ojalvo an Outside The Box Science Grant – congratulations!
Yohan Suryo Rahmanto, PhD is a postdoctoral fellow in the Department of Pathology at Johns Hopkins School of Medicine. His interest in the field of cellular metabolism and experimental therapeutics has led him to investigate ovarian cancer metabolism in the context of platinum drug resistance. In recurrent ovarian tumors, platinum resistance is a major concern and is responsible for the high disease mortality. The aim of the current project is to investigate the role of NOTCH3 in the metabolism of platinum resistant ovarian cancer cells. Outcome of these studies will improve our understanding on the mechanisms involved in the development of platinum resistant ovarian cancers, and also help to develop new therapeutic strategies from the metabolic perspective to combat this devastating disease. Dr. Rahmanto thank you for applying and winning an Outside The Box Science Grant – congratulations and we are thrilled to see your outcomes!
2014 Outside the Box Recipients
LINGLING XIAN, MD, PhD, is a research associate in the Department of Hematology at the Johns Hopkins Hospital, working in the laboratory of Dr. Linda Resar. Dr. Xian has a longstanding interest in cancer and stem cell biology and she is passionate about combining these two fields to discover novel, personalized therapies that target cancer stem cells for patients with ovarian cancer. Cancer stem cells, also known as tumor-initiator cells, are believed to be rare populations of tumor cells that hijack stem cell properties, which enable these cells to invade, spread to distant sites, and evade conventional chemotherapy. Dr. Xian’s project is based on the recent discovery that cancer cells derived from epithelial tissues can be “conditionally reprogrammed” into stem-like cells by culture under conditions similar to those used for embryonic stem cells. She proposes to derive conditionally reprogrammed cells (CRCs) directly from patient tumors and nonmalignant tissue as a personalized model for ovarian cancer stem cells. Next, she will screen these cells using a unique library of >3,000 drugs already approved for use in humans for agents that selectively kill CRCs from the ovarian cancers, but not normal tissue.
BLANCA VALLE, MD, PhD, is currently working in one of the leading laboratories in the field of epigenetics and translational research under the mentorship of Dr. David Sidransky and other successful investigators at Johns Hopkins. The objective of their project is to develop biomarkers for the early detection of ovarian cancer. The presence of promoter DNA methylation of particular genes in pre-malignant and malignant disease, and its lack in normal tissues, is promising for the development of biomarkers for early screening/diagnosis and prognosis. Such epigenetic changes can often be detected in blood and other bodily fluids, making it a feasible biomarker strategy for early detection of tumors. In this research project, she proposes to study promoter methylation of HIST1H2BB in tissues from ovarian cancer patients and it’s correlation to clinical outcome to assess its prognostic value. In addition, she aims to detect HIST1H2BB promoter methylation in blood and urine of ovarian cancer patients, as a first step to evaluate its viability as a diagnostic biomarker.
CHRISTIAN SCHUETZ, PhD, is a postdoctoral fellow in the Department of Pathology, Institute for Cell Engineering at the Johns Hopkins School of Medicine working in the Schneck/Oelke lab focusing on modulation of T-cell mediated anti-cancer immune responses and development of novel immunotherapy approaches, in which the body’s own immune cells are stimulated and trained to recognize and kill cancer cells. Increasing the in vivo activity of tumor‐specific T-cells will lead to clinically relevant anti‐tumor immune responses and subsequent enhancements in treatment outcomes and patient survival. During an immune response against cancer the majority of tumor infiltrating T-cells are often impaired due to tumor escape mechanisms, a situation that can be compared to driving a car with the parking brake on. Recent discovery of check point inhibitor molecules, such as anti-PD1, allow loosening this brake. Therefore, the major goal of this project is to reverse the non-responsiveness of ovarian cancer-specific T-cells through stimulation with particle-based artificial Antigen Presenting Cells (aAPC) that can not be manipulated by an immunosuppressive tumor environment. In combination with check point inhibitors, aAPC will be tested to overcome tumor escape mechanisms and to induce a potent and long lasting anti-ovarian cancer immune response in which the body’s own immune cells will recognize and destroy the patient’s tumor.
Low Grade Ovarian Cancer Grant
The single largest-ever grant awarded by HERA was given to Kwong K. Wong, Ph.D. of the MD Anderson Cancer Center. In this unique opportunity, Dr. Wong deciphered how insulin-like growth factor-1 (IGF-1) stimulates the growth of low-grade ovarian cancers. Read the interview with Dr. Wong.
Dr. Wong’s HERA-funded research has produced the following important results:
- New methods using the fully-sequenced human genome, known as “gene expression profiling,” were used to analyze low-grade ovarian cancers. Wong, et al found that very high amounts of an important hormone, IGF-1, were generated in low-grade ovarian cancers relative to other kinds of ovarian cancers or cancer precursors.
- The research also showed that when ovarian cancer cells are treated with the hormone IGF-1, activities of the protein “pAKT” increase in the cancer cells. This protein can be inactivated by known drugs. The Wong group is planning a clinical trial to test these drugs to treat low-grade ovarian cancer.
- Drs. King and Wong surveyed the drugs that interfere with IGF-1 and AKT functions in cancer and suggest drugs that may be effective in treatment of low-grade ovarian cancer. Download their survey here.
- With the pre-clinical data generated by the Wong Group, Dr. David Gershenson is planning a clinical trial to test these drugs to treat low-grade ovarian cancer, a cancer that is more chemoresistant and difficult to treat than its high-grade counterpart.
Download Dr. Wong’s findings on IGF-1 here.
- Nemanja Rodic, MD, PhD, is a postdoctoral research fellow in the Department of Pathology at Johns Hopkins, working in the Burns lab to understand the role of Long INterspersed Element-1 (LINE-1) in ovarian neoplasms. Dr. Rodic studied LINE-1 expression in ovarian cancers and identified new genomic LINE-1 insertions in ovarian cancer patients. (2013)
- Fnu Yu Yu, PhD, is a postdoctoral fellow in the Department of Pathology at the Johns Hopkins University School of Medicine. She examined the role of spleen tyrosine kinase that is highly upregulated in high-grade serous ovarian carcinoma. The goal of her study was to investigate the potential of targeting spleen tyrosine kinase as an effective strategy against this disease. (2013)
UPDATE ALERT 8.17.15!
Animal Study Shows Experimental Drug Combined with Standard Chemo May Shrink Treatment-Resistant Ovarian Cancers
Says Yu Yu about this high-profile publication, “This award from HERA [allowed] me to pursue the answers to several key questions that ultimately take us one step closer to understanding ovarian cancer and strategizing treatment options. Without the award, there is simply no answer, so I am truly thankful.”
- Ravi Anchoori, PhD, a Research Associate in the Department of Oncology at Johns Hopkins, worked on the interface of Chemistry and Biology to decipher the molecular mechanisms involved in regulated protein degradation. Dr. Anchoori developed a novel class of proteasome inhibitor and explored the effect of inhibiting the activity of the proteasome subunit ADRM1 that is specifically amplified in ovarian cancer. (2012)
- Elisabetta Kuhn, MD, a postdoctoral fellow in the Department of Pathology at Johns Hopkins, has dedicated her research career to ovarian cancer research with the hope of applying basic studies to improve clinical care of ovarian cancer patients. Dr. Kuhn studied laminin, a protein that is upregulated in ovarian cancer. She characterized laminin as a biomarker for serous tubal intraepithelial carcinoma, a putative precursor of ovarian serous cancer, to determine its biological functions in promoting cell growth and dissemination of precursor cells to ovary and other peritoneal tissues during tumor progression. (2012)
- Leonel Maldonado, MD, a postdoctoral fellow in the Department of Gynecology and Obstetrics at Johns Hopkins, studied the presence and function of Myeloid-derived suppressor cells (MDSCs) in subject-matched primary ovarian tumors and peripheral blood at the time of primary debulking surgery to determine whether the presence of MDSCs predicts response to standard platinum-taxol chemotherapy, and to determine whether inhibiting MDSC function can enhance effector T-cell function. (2012)
- Ana Isabel Tergas, MD, MPH, a postdoctoral clinical fellow in the Division of Gynecologic Oncology at Johns Hopkins, explored barriers to health care faced by a diverse group of ovarian cancer patients who underwent treatment at Johns Hopkins Hospital, and made recommendations for interventions aimed at mitigating these barriers. (2012)
- Jill Tseng, MD, a resident in the Department of Gynecology and Obstetrics at Johns Hopkins, studied a molecule present in ascites (excess fluid inthe abdomen) which inhibits the activation of certain immune cells and contributes to evasion of the immune system by ovarian cancer. (2011)
- Alexander Stoeck, Ph.D., a postdoctoral fellow in the Department of Pathology at Johns Hopkins University, studied Pbx1, a gene that is abnormally regulated in ovarian cancer to determine whether Pbx1 is a rational target for ovarian cancer therapies using a series of small compounds and genomic methods. (2011)
- Aimee Fleury, MD, a clinical fellow in the Kelly Gynocologic Oncology Service, studied how obesity effects risks associated with ovarian cancer surgery. (2011)
- Bin Guan, Ph.D., a post-doctoral fellow from the department of Pathology at the Johns Hopkins University, used state-of-the-art technologies to characterize the genes ARID1A and USP25 believed to play a role in ovarian and endometrioid cancer development. (2010)
- Ana Tergas, M.D., a clinical fellow from the Department of Gynecology and Obstetrics at the Johns Hopkins University, characterized the function of particular immune cells (NKT cells) and how they respond in ascites from ovarian cancer. (2010)
- Okey Ibeanu, M.D., M.P.H., a clinical fellow on the Kelly Gynecologic Oncology Service at the Johns Hopkins University, studied sexual dysfunction following primary surgery for ovarian cancer. (2010)
- Yuan Tian, Ph.D., of The Johns Hopkins Pathology Department and two-time recipient of the HERA OSB1 grant, conducted a study that profiles proteins modified with sugars from ovarian cancer patients. This innovative diagnostic approach will contribute to the design of therapeutics for specific cancers ovarian in origin. She identified molecular signatures for ovarian tumor sub-types and evaluated their utility to help in the prognosis and diagnosis of ovarian cancer. (2008 and 2009) This is a publication that resulted from her grant research: Identification of glycoproteins associated with different histological subtypes of ovarian tumors using quantitative glycoproteomics.
- Dan Lu, M.D., Ph.D., of the Department of Pathology at Johns Hopkins University studied gynecological tumor immunology and immune evasion. With the OSB1 award, she identified new molecules recognized by the immune system in ovarian cancer. Lu aimed to develop a more efficient screening methodology to identify cell surface molecules as target therapy of ovarian cancer. (2009) This is a publication that resulted from his grant research: Comparison of Candidate Serologic Markers for Type I and Type II Ovarian Cancer.
- Marie-France Penet, Ph.D., of the Russell H. Morgan Department of Radiology and Radiological Science at Johns Hopkins University developed a novel image-guided molecular targeted approach to ovarian cancer treatment. Therapeutic agents called “cationic liposomes” were designed to contain molecules that reduce specific proteins required for ovarian cancer cell growth. She previously developed similar innovative therapies that target breast and prostate cancer. (2009)
- Balasubramanyam Karanam M.D., Ph.D., from the Johns Hopkins Department of Oncology addressed epigenetic changes in ovarian cancer—these changes are stable between cell divisions, but do not involve changes in the underlying DNA sequence (like mutations). Using the activator and inhibitor molecules of these epigenetic changes, he determined the effects of the changes on regulation of ovarian cancer cell growth. (2008)
- Stephanie Ueda, M.D., of the Pathology Department at Johns Hopkins worked to understand the expression pattern of an enzyme proposed to be involved in the growth of low-grade ovarian serous carcinoma. She performed quantitative proteomics to identify molecules controlled by a protein found in ovarian cancer. (2008)
- Chih-long Chang, M.D., Ph.D., in the Pathology Department at Johns Hopkins proposed an immunotherapeutic approach for ovarian cancer. He determined if vaccinia virus, a virus that replicates in ovaries, could be genetically modified to express a protein that would improve immune responses to the ovaries. (2007)
- Natini Jinawath, M.D., Ph.D., in the Pathology Department at Johns Hopkins studied mutations in kinase enzymes in low-grade ovarian cancers. She tested inhibitors of these enzymes to assess their therapeutic potential. (2007)
- Rob Bristow, M.D., received a donor directed gift to the Department of Gynecology & Oncology at Johns Hopkins for training clinical fellows interested in pursuing research. (2007)
- Bryan Hennessy, M.D., at M. D. Anderson both characterized a number of ovarian cancer cell lines and started an “open access” ovarian cell line and information database. This resource is available to all scientists and will improve the quality of experiments performed. (2007)
- Tonya Webb, Ph.D., in pathology at Johns Hopkins worked to determine the function of cells from the immune system that infiltrate ovarian cancer. (2006) These are the publications that resulted from her grant research: Ascites Specific Inhibition of CD1d-Mediated Activation of Natural Killer T Cells; Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity.
- Martina Bazzaro, Ph.D., in pathology at Johns Hopkins University worked to develop a new test for early detection of ovarian cancer and to determine cellular abnormalities and potential growth inhibitors that target these abnormalities in ovarian cancer. (2004 and 2006) These are the publications that resulted from her grant research: Ubiquitin-Proteasome System Stress Sensitizes Ovarian Cancer to Proteasome Inhibitor–Induced Apoptosis; Myosin II Co-Chaperone General Cell UNC-45 Overexpression Is Associated with Ovarian Cancer, Rapid Proliferation, and Motility; Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor
- Antonio Santillan, M.D., in the department of gynecologic oncology at Johns Hopkins worked to individualize treatments for ovarian cancer. (2005) These are the publications that resulted from his grant research: Ubiquitin-Proteasome System Stress Sensitizes Ovarian Cancer to Proteasome Inhibitor–Induced Apoptosis; Myosin II Co-Chaperone General Cell UNC-45 Overexpression Is Associated with Ovarian Cancer, Rapid Proliferation, and Motility; Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor; and P53 Autoantibodies, Cytokine Levels and Ovarian Carcinogenesis.
- Kentaro Nakayama, M.D., Ph.D., in pathology at Johns Hopkins studied the molecular etiology of low-grade ovarian cancer and innovative target-based therapies. (2005)
- Two young scientists at M. D. Anderson Cancer Center received awards for novel collaborations with labs at different institutions to bring new technologies back to their labs to advance ovarian cancer research. (2005)
- Christina Borgeest, Ph.D., in public health at Johns Hopkins University explored the role of environmental factors like pesticides on estrogen metabolism. (2004)
- Hiroyuki Yoshida, M.D., Ph.D., in molecular therapeutics at M. D. Anderson Cancer Center worked to identify novel targets for controlling ovarian cancer metastases. (2004)
- Brant Wang, M.D., of Johns Hopkins University worked toward an early detection test and improving the diagnosis value of the CA 125 blood test. (2003)