2018-2019 Hillman Fellows for Innovative Cancer Research Program

Building on our long and fruitful partnership with Hillman Family Foundations, we at UPMC Hillman Cancer Center are honored to embark upon a new era of collaboration through the recently redesigned Hillman Fellows for Innovative Cancer Research Program. Over the next ten years, Henry L. Hillman Foundation has pledged a significant investment in our comprehensive program, with the goal of supporting several key areas that are of strategic importance to our mission of reducing the burden of cancer. Areas supported by this program include recruitment of top-tier senior and early-career faculty, as well as funding of highly innovative developmental research projects and transdisciplinary collaborative research efforts. The program also supports a new competitive opportunity for postdoctoral candidates, which is currently accepting applications (see: www.UPMCHillman.com/PostdoctoralFellowship).

We are excited to announce the new Hillman Fellows for Innovative Cancer Research for the award period of July 1, 2018 through June 30, 2019.

Hillman Fellows for Innovative Cancer Research

A key priority of UPMC Hillman Cancer Center is the recruitment of exceptional faculty across multiple research areas, including the recruitment of senior-level investigators of national and international renown who will serve in visionary leadership positions within the institution. After national searches, two highly accomplished individuals have joined the faculty to lead Hillman research programs as 2018 Hillman Fellows:

Ronald Buckanovich, MD, PhD, arrived in September 2017 as Professor of Medicine and of Obstetrics, Gynecology and Reproductive Sciences as well as Co-Leader of Hillman Breast and Ovarian Cancer Program and Co-Director of the UPMC Ovarian Cancer Center of Excellence. In addition, he was recently appointed as Co-Director of the Women’s Cancer Research Center, which is a collaboration between UPMC Hillman Cancer Center and Magee-Womens Research Institute. Dr. Buckanovich is playing an integral role in establishing a Comprehensive Ovarian Biology Research Center, which brings together biology and oncology researchers to study the molecular and physiological factors that mediate the development of ovarian cancer, his area of expertise.

Shou-Jiang (SJ) Gao, PhD joined the faculty in April 2018 as The Pittsburgh Foundation Endowed Chair in Drug Development for Immunotherapy, Professor of Microbiology and Molecular Genetics, and Leader of the Hillman Cancer Virology Program. A leading expert in tumor virology, Dr. Gao developed the first genetic system for studying Kaposi’s sarcoma-associated herpesvirus (KSHV), as well as several KSHV infection and cellular transformation models, which were used to define the mechanisms of KSHV infection and oncogenesis. This work has led to the identification of numerous targeted and immunotherapy-based strategies for treating KSHV-induced cancers.

Hillman Fellows for Innovative Early-Career Cancer Research

As a way to augment current research strengths and enhance expertise in new and promising disciplines, we have recruited three exceptional junior investigators to UPMC Hillman Cancer Center who will begin their academic careers as Hillman Fellows:

Lan Coffman, MD, an Assistant Professor of Medicine and a member of the Hillman Breast and Ovarian Cancer Program, specializes in the treatment and study of ovarian cancer. She is particularly interested in understanding how carcinoma-associated mesenchymal stem cells (CA-MSCs) develop within the tumor microenvironment (defined as the area surrounding the tumor that contains blood vessels and immune and stromal cells), and how they act to promote ovarian cancer growth. Recent findings in her laboratory demonstrated that cancer cells act to transform normal mesenchymal stem cells into CA-MSCs by inducing epigenetic modifications to DNA that lead to alterations in gene expression (i.e., the amount of protein-coding RNA that gets transcribed).

Hung Luu, MD, PhD, MPH is an Assistant Professor of Epidemiology and a member of the Hillman Cancer Epidemiology and Prevention Program. Dr. Luu’s research applies advanced molecular technologies to the investigation of genetic and environmental factors that influence cancer development, with the ultimate goal of translating new discoveries into improved methods of cancer prevention and treatment.

Yana Najjar, MD is an Assistant Professor of Medicine, a member of the Hillman Melanoma Program, and a medical oncologist specializing in the treatment of melanoma. Her research focuses on cancer immunotherapy and its impact on the tumor microenvironment and peripheral immune system.

Hillman Fellows for Innovative Developmental Cancer Research

Developmental high-risk/high-reward projects hold the greatest promise for new discoveries that could eventually reshape medical practice. To promote groundbreaking research, our Hillman Fellows program will support eight cancer pilot projects that were chosen after a Cancer Center-wide solicitation of proposals. The Cancer Center leadership selected these projects, which span the breadth of novel research being done at Hillman, based on their scientific merit, innovation, significance, and approach.

Maninjay Atianand, PhD, Assistant Professor of Immunology: Long noncoding RNAs as regulatory checkpoints in tumor-associated macrophages

In this pilot project, Dr. Atianand’s laboratory will determine the role of long noncoding RNAs (lncRNAs) (RNA transcripts that do not get translated into proteins) in controlling immune cell functions in the tumor microenvironment. In particular, his team will characterize the expression of the lncRNAs found in tumor-associated macrophages in melanoma, and explore their role in antitumor immunity using mouse models. It is anticipated that these studies will reveal new translational targets as well as biomarkers that predict response to cancer immunotherapies.

Randall Brand, MD, Professor of Medicine and of Human Genetics and a member of the Hillman Cancer Epidemiology and Prevention Program: Characterization of chromatin environment on cancer risk and inflammation in Lynch Syndrome

Individuals with Lynch Syndrome harbor a mutation in at least one of the main DNA repair genes, greatly increasing their risk for colorectal cancer (CRC). However, not everyone with these mutations will develop CRC. This pilot project aims to understand changes in how DNA is packaged with RNA and histone proteins in response to environmental stressors/inflammatory stimuli in Lynch Syndrome patients, and the relationship of these changes to cancer risk. This project will facilitate the development of novel cancer prevention approaches and the identification of new surrogate markers to evaluate the efficacy of preventive agents. The long-term goal is to personalize CRC prevention by identifying biomarkers associated with cancer risk that can be easily monitored and applied to not only individuals with Lynch Syndrome, but to the general population as well.

Xin Huang, PhD, Assistant Professor of Obstetrics, Gynecology, and Reproductive Sciences and a member of the Hillman Breast and Ovarian Cancer Program: miR-210 function in clear cell renal cell carcinoma

The hypoxia responsive pathway, normally induced by low oxygen, is nearly always upregulated (i.e., increased) in clear cell renal cell carcinoma (ccRCC), making its components attractive therapeutic targets. Dr. Huang’s laboratory found that hypoxia induces robust expression of a particular molecule, microRNA (miR)-210, in a variety of cancerous cell lines through the RNA transcription regulating factors hypoxia-inducible factors (HIF) 1-alpha and 2-alpha. Notably, miR-210 is one of the most highly expressed miRNAs in ccRCC as compared with normal tissue, and its overexpression correlates with poor overall patient survival. Based on this evidence and the fact that microRNA can alter cell activity through silencing of gene expression, the Huang laboratory seeks to delineate the role of miR-210 in ccRCC tumorigenesis as well as test its potential as a therapeutic target in this pilot project.

Bruce Jacobs, MD, MPH, Assistant Professor of Urology: Effects of cancer care centralization on geographic, racial, ethnic and socioeconomic disparities

In recent decades, health care delivery for patients with cancer has undergone a dramatic shift whereby care is increasingly centralized in ‘centers of excellence’ with high patient volume. This shift has an immense potential to improve patient outcomes, since many studies suggest that high-volume centers demonstrate improved survival. Although centralization appears to improve outcomes for patients receiving care at these high-volume centers, the overall effects of centralization remain unknown. The goal of Dr. Jacob’s pilot project is to determine the impact of centralization on the cancer care received by subgroups of patients who differ with respect to geographic location, race, ethnicity, and socioeconomic status.

Xinghau Lu, MD, PhD, Professor of Biomedical Informatics and a member of the Hillman Molecular and Cellular Cancer Biology Program: Developing an artificial intelligence-based clinical decision support system for precision oncology

The pilot project from the Lu laboratory aims to develop artificial intelligence methods to assist clinical decision making. The investigators will collect clinical data from non-small cell lung cancer (NSCLC) patients treated at UPMC Hillman Cancer Center to discover how patterns of treatment influence clinical outcomes in patients with specific characteristics. The overarching goal is to use such information to develop decision support systems enabling oncologists to personalize therapies for each individual NSCLC patient.

Roderick O’Sullivan, PhD, Assistant Professor of Pharmacology and Chemical Biology and a member of the Hillman Molecular and Cellular Cancer Biology Program: Effects of telomerase inhibition in neuroblastoma

Telomerase is the specialized enzyme responsible for de novo synthesis of new telomeric DNA at chromosome ends. Increased expression (amount) and activity of telomerase is a defining hallmark of cancer cells, whereas normal cells rarely express it, fueling the hypothesis that telomerase inhibition is an Achilles’ heel for cancer. The goal of this pilot project is to adapt and apply a highly innovative CRISPR-Cas9-based gene editing strategy to rapidly, yet reversibly, remove telomerase from cancer cells and decipher the effects of telomerase inhibition in a clinically relevant model of neuroblastoma (a type of brain cancer diagnosed in both adults and children).

Shilpa Sant, PhD, Assistant Professor of Pharmaceutical Sciences and member of the Hillman Breast and Ovarian Cancer Program: Role of pathological microcalcifications in the primary tumor progression

Breast cancer is frequently detected by the presence of calcium deposits (microcalcifications) seen on mammograms. Studies suggest that the microcalcifications are a risk factor for breast cancer progression, but whether they cause or are just a result of the disease remains unknown. However, there does appear to be a link between microcalcifications, specifically those with the calcium-containing mineral hydroxyapatite, and cancer cells acquiring a mesenchymal phenotype (cells that gain the migratory and invasive properties needed for metastasis). Moreover, evidence suggests a link between microcalcifications and breast cancer cells overexpressing bone markers and metastasizing to the bone. In this pilot project, the Sant laboratory will develop in vitro and in vivo approaches to elucidate the functional role that microcalcifications may play in tumor invasion, bone mimicry and subsequent risk of bone metastasis.

Shivendra Singh, PhD, UPMC Chair in Cancer Prevention Research, Professor of Pharmacology and Chemical Biology and of Urology, Hillman Associate Director for Basic Research, and member of the Hillman Breast and Ovarian Cancer and Cancer Epidemiology and Prevention Programs: A novel strategy for prevention of breast cancer-induced osteolytic bone resorption

Osteolytic bone erosion leading to pain is a serious complication in women with metastatic breast cancer. The goal of this project is to determine the activity of a novel plant-based regimen in preventing bone erosion.

Hillman Fellows for Innovative Team Science Cancer Research

The ability to move the cancer field forward often requires a multi-disciplinary approach. Medical oncologist, cancer epigenetics researcher, and Leader of the Hillman Lung Cancer Program, James Herman, MD, has teamed up with cancer epidemiologist and Co-Leader of the Hillman Cancer Epidemiology and Prevention Program, Jian-Min Yuan, MD, PhD, and pulmonologist David Wilson, MD, MPH, on the Pittsburgh Lung Cancer Screening Study (PLuSS), a community-based research cohort of current and ex-smokers, screened with low-dose helical computed tomography (CT) and followed for development of lung cancer since 2002. PLuSS has provided the basis for continual improvements in CT screening for individuals at high risk for developing lung cancer, a method that has been shown to reduce lung cancer mortality. In addition to the CT scan results, biological fluids including blood, sputum, and urine are collected from study participants, and provide an invaluable resource for Hillman investigators to conduct a wide range of research studies, such as genome-wide analysis of molecular changes in lung cancer, and the development of novel cancer biomarkers for further-improved detection (i.e., fewer false positives and false negatives with screening), diagnosis, and therapeutic monitoring. This project was selected for support through the Hillman Fellows Program by Cancer Center leadership due to its potential for high impact and reach across our vast community network.