New postdoctoral training program at Hillman

We at UPMC Hillman Cancer Center are pleased to announce a new and exciting postdoctoral training opportunity. Made possible by a generous donation from Henry L. Hillman Foundation, the Hillman Postdoctoral Fellows for Innovative Cancer Research program seeks the nation’s top graduate students and early-stage postdoctoral fellows to pursue cutting edge cancer research.

This very competitive program will provide fellows with a stipend (20% above the current NIH level) and a generous career development fund. Fellows will choose their mentors from nearly 70 nationally and internationally known faculty whose research spans seven thematic areas: biobehavioral oncology, cancer biology, cancer epidemiology and prevention, cancer immunology and immunotherapy, cancer therapeutics, cancer virology, and genome stability.

The University of Pittsburgh is a world-class research institution that currently ranks in the top five in the nation for NIH funding and the city of Pittsburgh is recognized for its livability and culture. Pittsburgh offers many vibrant neighborhoods with affordable housing, award-winning cuisine, and interesting cultural events, and was recently rated as the second-best city for millennials.

The application deadline for this program is August 31, 2018. Please see the website www.UPMCHillman.com/PostdoctoralFellowship for details on how to apply.

Watch Dr. Christopher Bakkenist, the Associate Director of Education and Training for UPMC Hillman Cancer Center, describe this new program.

Hillman Researcher shows that the proapoptotic protein PUMA also enhances necroptosis

Multiple classes of chemotherapeutic drugs work by inducing cancer cell death, but these drugs are often ineffective in treating cancer patients. Dr. Lin Zhang, Professor of Pharmacology and Chemical Biology, seeks to improve treatment outcome by studying the mechanisms underlying both drug-mediated cytotoxicity and cancer cell resistance to these drugs.

The Zhang laboratory is particularly interested in PUMA (p53 upregulated modulator of apoptosis), a protein upregulated by multiple anticancer drugs that promotes programmed cell death, otherwise known as apoptosis. In a paper recently published in the Proceedings of the National Academy of Sciences, they showed that PUMA also plays a key role in enhancing necroptosis, a type of programmed necrotic cell death associated with inflammation. In their study, stimulation of necroptosis in cancer cells led to upregulated PUMA expression, triggering release of mitochondrial DNA into the cytosol and further necroptotic cell death in a positive feedback loop. Unlike apoptosis, necroptosis engages the immune system to eliminate dead cell debris. Thus, PUMA has the potential to both amplify the death signal and to promote cancer immunity. Dr. Zhang hopes to build upon this work to improve cancer therapy and develop PUMA as a biomarker for treatment response.

Watch Dr. Zhang discuss his research in the video.

Clinical Trials at UPMC Hillman Cancer Center

Basic and translational researchers at UPMC Hillman Cancer Center work closely with physician-scientists and clinicians to quickly move the most promising research results from their labs into clinical trials. While the conduct of clinical studies provides critical information to researchers that can be taken back to the lab for further study and improvement, they also provide patients with early access to the most cutting-edge and innovative cancer treatments available.

Watch Edward Chu, MD, Deputy Director of UPMC Hillman Cancer Center, Chief of Hematology-Oncology, and Co-Leader of the Hillman Cancer Therapeutics Program, discuss how clinical trials are advancing the way cancer patients are treated.

Pitt and UPMC Launch New Immune Transplant and Therapy Center (ITTC)

On February 13, Pitt and UPMC leaders announced plans to establish the new UPMC Immune Transplant and Therapy Center (ITTC), with much of its activity planned within an eight-story innovation hub—all part of a concerted effort to harness the power of the human immune system to treat and cure a wide range of diseases. As part of the collaboration, UPMC has made a $200 million commitment to ITTC, and the University will transform a century-old building at 5000 Baum Boulevard into a world-class space for labs, offices, startup companies, and industry partners.

Backed by decades of pioneering research at Pitt, UPMC’s initial three-year funding commitment for ITTC seeks to dramatically accelerate the pace at which medical teams can utilize new research. This investment will help pinpoint the most promising advances in immunology that are capable of enhancing human health. The center’s work will initially focus on three major areas: cancer, aging and chronic diseases, and transplantation.

Watch the video and visit the ITTC website to learn more.

Hillman Researcher Aims to Target Colorectal Cancer with a Multifaceted Approach

Colorectal cancer (CRC) is a leading cause of cancer death in the United States and worldwide. While common oncogenic mutations in CRC have been identified, attempts to target these pathways have had limited success.

Jian Yu, PhD, Professor of Pathology and Radiation Oncology, is an expert in colon cancer biology and the signaling mechanisms that promote cancer cell growth and drug resistance. She was recently awarded a new R01 grant from the National Cancer Institute to examine the role of the eIF4E protein in colon cancer initiation and progression. Her preliminary data suggests that eIF4E can influence a cancer cell’s ability to grow despite stressful conditions through metabolic adaptation in which it can become “addicted” to certain nutrients. Targeting this metabolic pathway in concert with other pathways that induce cancer cell death and elicit an immune response could improve outcomes for colon cancer patients. Another related area of investigation in her lab is focused on developing methods to protect normal, healthy intestinal stem cells from cancer treatments, which would further improve therapeutic index and reduce side effects.

Watch the video to learn more about Dr. Yu’s research.

Ovarian Cancer Cells Manipulate Surrounding Normal Cells to Aid Tumor Growth

Tumors do not grow in isolation, but are surrounded by a rich microenvironment that contains blood vessels, fibroblasts, immune cells, and a multitude of other components. Cancer cells can influence their microenvironment through extracellular signaling mechanisms to enable and/or enhance their ability to grow and metastasize, such as through the promotion of angiogenesis and immune tolerance.

Lan Coffman, MD, PhD, Assistant Professor of Medicine, is a medical oncologist and researcher who specializes in ovarian cancer. She is particularly interested in understanding how carcinoma-associated mesenchymal stem cells (CA-MSCs) develop within the tumor microenvironment, and how they act to promote ovarian cancer growth. Recent findings in her laboratory demonstrated that cancer cells are able to transform normal mesenchymal stem cells into CA-MSCs through epigenetic alterations.

To learn more, watch Dr. Coffman discuss her research in the video.

Multispectral Tumor Imaging May Guide Precision Immunotherapy

While novel immunotherapies are revolutionizing the way some cancers are treated, not all patients will respond to treatment, underlining the need for biomarkers that can predict potential clinical benefit and monitor a patient’s response.

Until recently, immune activity within and surrounding a tumor was typically analyzed through staining of an individual biomarker on a pathological slide, or though cell sorting and analysis of a homogenized tumor sample. New technology available at UPMC Hillman Cancer Center’s Immunologic Monitoring and Cellular Products Laboratory (IMCPL) now enables multispectral automated imaging of intact tumor tissues, allowing for the rapid detection and quantitation of multiple overlapping biomarkers and simultaneous evaluation of their spatial context within the tissue architecture.

Watch Lisa Butterfield, PhD, Professor of Medicine, Surgery and Immunology; Director of the Hillman IMCPL; and President of the Society for Immunotherapy of Cancer (SITC) describe the importance of this new technology in informing and guiding precision cancer immunotherapy going forward.

Combination Targeted Therapy Improves Survival of Stage III Melanoma Patients

It is estimated that 40% of melanomas contain BRAF mutations that promote cancer cell growth. While previous studies have shown that treatment with the combination of inhibitors targeting BRAF (dabrafenib) and MEK (trametinib) improved survival in patients with advanced, unresectable metastatic BRAF-mutant melanoma, it was not clear whether this combination would have the same effect in an adjuvant setting.

A team led by John M. Kirkwood, MD, Thomas and Sandra Usher Professor of Medicine, Dermatology and Translational Science, conducted a phase III, double-blind, randomized clinical trial in patients with stage III, BRAF-mutated melanoma whose tumors had been surgically removed, and found that the adjuvant use of combination therapy with dabrafenib plus trametinib for 12 months resulted in a 53% lower risk of relapse compared to placebo. At 3 years, the rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group. These results were recently reported in the New England Journal of Medicine and presented at the annual meeting of the European Society for Medical Oncology (ESMO).

Watch Dr. Kirkwood discuss this study and its potential impact in the video.

Hillman Legacy Lives On at UPMC Hillman Cancer Center

Through Hillman Foundation and Henry L. Hillman Foundation, the late Henry and Elsie Hillman made generous contributions throughout the Pittsburgh region, especially in science and medicine. Their vision of making Pittsburgh a renowned leader in cancer care became a reality in 2002 with a $10 million grant to establish the Hillman Cancer Center, a world-class institution housing both research laboratories and clinical treatment facilities under one roof. Their generous support of the Hillman Fellows for Innovative Cancer Research Program, established in 2004, has helped to attract promising young researchers and to foster the development of novel cancer treatments. The Hillman Fellows Program will continue to grow and flourish, with a newly announced commitment of $30 million from Henry L. Hillman Foundation to support the Program over the next 10 years.

Watch Stanley Marks, MD, Chairman of UPMC Hillman Cancer Center, and Robert L. Ferris, MD, PhD, Director of UPMC Hillman Cancer Center, discuss the Hillman vision and legacy in the video.

Prestigious Federal Contract Supports Drug Pharmacology Studies at Hillman

Last August, UPMC Hillman Cancer Center became one of only two academic centers in the nation to secure a competitive contract from the National Cancer Institute (NCI) to perform preclinical and clinical pharmacology research critical to the development of new cancer drugs. Led by Jan Beumer, PharmD, PhD, DABT, Associate Professor of Pharmaceutical Sciences and Medicine, and Director of the Hillman Cancer Pharmacokinetics and Pharmacodynamics Facility, this award could bring up to $9.9 million in research projects to Hillman over five years.

Dr. Beumer’s laboratory evaluates the formulation, dosing, pharmacokinetics, efficacy, and toxicity of new drugs prior to their use in phase I (“first-in-human”) clinical trials, to inform routes and doses for drug delivery as well as to predict potential effects of the drug in patients. Through this NCI contract, Dr. Beumer also performs pharmacokinetic analysis in support of clinical trials.

Watch Dr. Beumer discuss his research further in the video, and learn more here and here.

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