Medicine and Health Sciences Commons^™

Novel Oncogenic Transcription Factor Cooperation In Rb-Deficient Cancer, Amy C. Mandigo, Ayesha A Shafi, Jennifer J Mccann, Wei Yuan, Talya Laufer, Denisa Bogdan, Lewis Gallagher, Emanuela Dylgjeri, Galina Semenova, Irina A Vasilevskaya, M J Schiewer, Chris M Mcnair, Johann S De Bono, Karen E Knudsen

Department of Cancer Biology Faculty Papers

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome …

Principles Of Hypotensive Shock: A Video Introduction To Pathophysiology And Treatment Strategies, Brittany Macdonald, Nicholas Macdonald, Jacob Garcia, Xiao Chi Zhang, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

Audience: Emergency medicine interns, medical students, and mid-level providers (physician assistants, nurse practitioners).

Introduction: Shock is defined as a state of global tissue hypoxia and is typically the result of hypotension and circulatory system failure. A variety of disease states may ultimately culminate in hypotensive shock through one or more generally recognized mechanisms – hypovolemic, cardiogenic, obstructive, and/or distributive shock. These mechanisms differ significantly in terms of their pathophysiology and requisite treatment. While the effects of hypotensive shock are initially reversible, untreated hypotensive shock may rapidly progress to multiorgan failure and death. Hence, the ability to promptly recognize a state …

When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects Among Individuals With Cancer And Their Caregivers, Brandy-Joe Milliron, Lora Packel, Dan Dychtwald, Cynthia Klobodu, Laura Pontiggia, Ochi Ogbogu, Byron Barksdale, Jonathan Deutsch

Institute of Emerging Health Professions Faculty Papers

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced …

Atypical Ataxia Presentation In Variant Ataxia Telangiectasia: Iranian Case-Series And Review Of The Literature, Tannaz Moeini Shad, Reza Yazdani, Parisa Amirifar, Samaneh Delavari, Marzieh Heidarzadeh Arani, Seyed Alireza Mahdaviani, Mahnaz Sadeghi-Shabestari, Asghar Aghamohammadi, Nima Rezaei, Hassan Abolhassani

Department of Neurology Faculty Papers

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which …

Thomas Jefferson University Research - Convergent Thinking, Creative Application

Thomas Jefferson University Research Magazine

One way we accomplish our distinctive programmatic approach to research is by organizing as multidisciplinary centers and institutes around specific challenges. Led by visionaries and staffed by experts, these entities enable us to more quickly move discovery to translation and application; and they are excellent environments for training colleagues and students to address the practical challenges the world presents.

Sending Jefferson Research To Space

Thomas Jefferson University Research Magazine

Three of Jefferson’s collaborative research projects will become part of the upcoming Rakia space mission, the first-ever private mission to the International Space Station. Scheduled for early 2022, Rakia will include 44 research projects to help scientists explore topics including the effects of low-gravity and space travel on the human body.

“The Rakia mission selected all three of the projects submitted by Jefferson and its institutional collaborators—Sheba Medical Center, the Ramon Foundation and the Israeli Space Agency at the Ministry of Science and Technology,” explains Zvi Grunwald, MD, James D. Wentzler Professor of Anesthesiology and executive director of the Jefferson …

Anticipating Risk For Joint Replacement Problems

Thomas Jefferson University Research Magazine

Research teams led by Javad Parvizi, MD, clinical research professor and vice chair of orthopedic surgery, have identified risk factors associated with two major postoperative issues for patients undergoing total hip or knee replacements.

Despite ongoing improvements in technology and perioperative protocols, some patients undergoing total joint arthroplasty (TJA) experience serious medical complications requiring postoperative intensive care. With TJA increasingly being performed in ambulatory surgical settings, it is important to understand which patients are most at risk for such complications. Dr. Parvizi and his colleagues conducted a study to identify patient risk factors for admission to an intensive care unit …

Jeffsolves With Student Innovation

Thomas Jefferson University Research Magazine

The JeffSolves MedTech program teams industrial design and medical students to develop innovative solutions to specific healthcare problems. Having chosen particular, concrete challenges faced by medical patients, student teams collaborate to conduct in-depth user research and problem identification, develop potentially marketable solutions and create prototype products. “The solutions these teams create are consistently remarkable and effective,” says Bon Ku, MD, assistant dean for health and design at Sidney Kimmel Medical College.

A Design For Mitigating Patient Hypothermia

Thomas Jefferson University Research Magazine

General anesthesia during surgery can impair the body’s autonomic temperature regulation and lead to patients having dangerously low body temperature. That, in turn, increases an array of clinical risks, including poor wound healing and infection, excess blood loss, cardiac arrhythmias and impaired renal function. Unfortunately, current surgical gowns— which have very little thermal capability—provide no significant protection against heat loss.

For that reason, a cross-disciplinary team of Jefferson students and faculty—with expertise in anesthesiology, mechanical engineering, textile engineering, textile technology and fashion design—is creating a new type of patient garment that is intended to mitigate the problem of surgically related …

Does Art Reduce Bias Among Healthcare Providers?

Thomas Jefferson University Research Magazine

Katherine Cambareri, who earned an MPH from Jefferson in 2019, works as a clinical research coordinator at Children's Hospital of Philadelphia. She is also a serious photographer and deeply interested in exploring the synergies between public health and art.

In 2016, Cambareri created a photographic exhibition by documenting the clothes worn by survivors of sexual violence when they were assaulted. The exhibit’s photographs—individually straightforward, collectively powerful—were created with the intention of increasing understanding of sexual assault and challenging false assumptions of those who blame the victim. The exhibition titled “Well, What Were You Wearing?” has been presented across the country …

Measuring Empathy Among The Healthcare Team

Thomas Jefferson University Research Magazine

We live in a time when empathy seems more important than ever. Two recent studies assess opportunities and challenges for training physicians and nurses to develop stronger skills in empathy.

Jefferson research professor of psychiatry and human behavior Mohammadreza Hojat, PhD, led a nationwide study of empathy in nearly 11,000 osteopathic medical students in the United States. The study used the Jefferson Scale of Empathy (JSE), a validated measurement tool developed at Jefferson and used in 85 countries and translated into 56 languages. Among its findings were that women tended to score higher on the empathy scale than men, and …

Canine Intervention For Ptsd

Thomas Jefferson University Research Magazine

Strong anecdotal evidence suggests that trained service dogs can help mitigate symptoms of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). In particular, they may help reduce incidence of substance abuse and suicide in military veterans with PTSD and TBI. Two Jefferson College of Nursing faculty members— assistant professor Jennifer Shiroff, PhD, and instructor Jacquelyn O’Rourke-Fulford, MSN— have begun the process of formally assessing the effectiveness of service dogs as a therapeutic intervention for veterans with PTSD or TBI.

Assessing Trauma’S Effects On Children

Thomas Jefferson University Research Magazine

“Children who are exposed to adverse experiences early in life may not think, feel or behave the same way that typically developing children do,” says Kirby L. Wycoff, PsyD, associate professor of counseling and behavioral health and director of Jefferson’s Community and Trauma Counseling program. “If behavioral health professionals are not cognizant of the effects of trauma in the lives of children, they may actually be providing ineffective and inefficient care—and doing a disservice to the children and their families.”

Brain Implant Aims To Restore Movement After Stroke

Thomas Jefferson University Research Magazine

In the United States, someone has a stroke every 40 seconds. Often, these victims have long-term physical disabilities—the inability to use an arm and hand properly, for example. While rehabilitation can restore some function, improvements typically plateau well short of full recovery. Seeking to help stroke patients gain a fuller return-to-function, a research group led by assistant professor of neurology Mijail Serruya, MD, PhD, has begun a clinical trial of a brain implant and motorized robotic brace that could enable greater mobility. The work represents a convergence of disciplines, including computer science, fashion design, mechanical engineering, neurology, physics and rehabilitation …

Immune Signals In Parkinson’S Disease

Thomas Jefferson University Research Magazine

The Jefferson Comprehensive Parkinson’s Disease Center is one of the Parkinson’s Foundation’s 33 Centers of Excellence in the United States. Its director, Richard Smeyne, PhD, professor of neuroscience, and his research group are examining the cell signaling and cascade of events that leads to initiation of Parkinson’s disease (PD), seeking important clues about ways to arrest the condition’s progression. Mutation within the Leucine-rich Repeat Kinase 2 (LRRK2) gene is thought to underlie about 20 percent of all PD cases. Two of the group’s recent studies suggest that immune signaling from T-cells and B-cells in the blood plays an unexpected and …

How Does Calcium Impact Cardiac Mitochondria?

Thomas Jefferson University Research Magazine

The ability of a cardiac cell to work hard and continuously depends on the energy-producing function of its mitochondria. Calcium is key to proper mitochondrial function—but only in the right amounts. Too much calcium leads to cell death; too little suppresses production of the fuel a cell needs to function.

Research collaborators Shey-Shing Sheu, PhD, professor of medicine, and Gyorgy Csordas, MD, research associate professor of pathology, anatomy and cell biology, are studying the mechanisms by which cardiac mitochondria use calcium and other molecules. And they are shedding light on how dysfunction in those mechanisms contribute to ischemic heart disease, …

Paradigm-Changing Immunotherapy For Multiple Sclerosis

Thomas Jefferson University Research Magazine

In multiple sclerosis (MS), the body’s immune system attacks the myelin sheath, the protective layer surrounding nerve axons. Current MS therapies act by suppressing the immune system broadly—with sometimes serious side effects, including infection and cancer. However, a team of researchers led by Abdolmohamad Rostami, MD, PhD, professor and chair of neurology, has found a way to prevent immune cells from attacking myelin—while leaving the rest of the immune system intact. In mouse models of MS, their approach has halted disease progression.

Studying Hiv Antiretroviral Therapy

Thomas Jefferson University Research Magazine

Combination antiretroviral therapy (ART) has turned HIV infection into a treatable, chronic condition, rather than one that is almost inevitably fatal. As a result, as they age, people with HIV often begin taking other medications to treat medical conditions ranging from heart disease to gastrointestinal problems to cancer. The increased number of medications creates a risk for drug-drug interactions. Jason Schafer, PharmD, professor and vice chair of pharmacy practice, is exploring combinations of ART drugs that can reduce the number and severity of those interactions.

Exploring Dna Damage Repair

Thomas Jefferson University Research Magazine

A cell’s ability to repair damaged DNA is key to its maintaining normal biology and protecting against cell death. But the repair process can be a two-sided coin: keeping a normal cell healthy is beneficial; keeping a malignant cell healthy can promote cancer. The mechanisms by which cells recognize and attempt to repair damage are myriad and complex; and individual DNA-repair proteins can be involved in multiple pathways. Jefferson researchers across several fields are working to understand the genomic and molecular processes at work in DNA repair—and the problems created when those processes go awry.

Images Of Exploration And Discovery

Thomas Jefferson University Research Magazine

There are many ways of capturing the phenomenon and processes that biomedical researchers investigate. Steady advances in imaging technologies provide windows into microscopic forms and functions—views that can be appreciated, in different ways, by scientists and nonscientists alike. Here are a small sample of the images that emerge from the work of Jefferson researchers

Reinvigorating Immune Response To Advanced Melanoma

Thomas Jefferson University Research Magazine

Melanoma represents a small fraction of skin cancerrelated malignancies, yet accounts for the majority of its mortalities—and the incidence of cutaneous melanoma is rising. While treatments using smalltargeted inhibitors and immune checkpoint antibodies have increased long-term survival in advancedstage cutaneous melanoma, many patients still do not realize any benefit from the treatments. Another group of patients initially have beneficial results but ultimately find their disease progressing, in part due to cancer cells’ acquired resistance to immune response. And still other patients have difficulty with the treatment’s high toxicity.

Emad Alnemri, PhD, Thomas Eakins Professor of Biochemistry and Molecular Biology, and …

Attacking Cancer With Immunotherapies

Thomas Jefferson University Research Magazine

Jefferson scientists and clinicians continue to advance new approaches for cancer therapies. Two potential immune-prompting treatments—one for solid tumors and advanced non-small-cell lung carcinoma, and a second for recurrent gastrointestinal tumors—entered clinical trials in fall 2020.

The first drug is based on multi-functional immunorecruitment protein based on a fusion protein platform developed by Mark Tykocinski, MD, Jefferson provost and Anthony F. and Gertrude M. DePalma Dean of Sidney Kimmel Medical College. Created through the chimerization of proteins with carefully selected characteristics, the treatment is designed to have a two-part action: first, disabling cancer cells’ ability to camouflage themselves from the …

Computational Intelligence On Eye Disease

Thomas Jefferson University Research Magazine

“The use of big data in research holds enormous potential for improving public health and healthcare delivery, generating new knowledge more quickly than traditional scientific approaches, and providing a holistic understanding of specific illnesses,” says Amna Al-Alawi, DM, who recently completed her Doctor of Management degree from Jefferson’s Strategic Leadership program. “Ultimately, I believe it can offer enhanced care so that practitioners can understand more accurately the patient’s unique combination of genes, environmental risks and disease phenotype, which can help detect certain diseases at an earlier stage.”

Examining Healthcare Mutual Fund Performance

Thomas Jefferson University Research Magazine

Specialty mutual funds such as healthcare funds offer investors the opportunity to focus on high total return, income and further diversification within a specific industry. Although extensive research has been conducted on mutual fund performance generally, little such work has been conducted on healthcare-related mutual funds.

D.K. Malhotra, PhD, professor of finance and Nydick Family Term Chair and colleagues, sought to decode the characteristics and performance of healthcare mutual funds by examining their risk-adjusted rate of return from 2001 to 2018. He studied a broad range of healthcare-related funds, including those that focused on pharmaceuticals, biotechnology, health insurance, manufacture of …

Cold-Brew Chemistry

Thomas Jefferson University Research Magazine

Despite the growing consumption of cold-brew coffee around the world, little is known about the drink’s chemical makeup. Three researchers are helping to fill that gap with new findings on its level of beneficial antioxidants.

A recent study by Niny Rao, PhD, associate professor of chemistry, Megan Fuller, PhD, former assistant professor of chemistry and pre-medical studies student Meghan Grim found that the healthpromoting antioxidants in cold-brew coffee can differ significantly from traditional hot-brew coffee prepared with the same beans, particularly for dark roasts. While similar amounts of antioxidants were observed in hot and cold preparations made from lighter-roast coffee …

Fast-Paced, Frontline Research

Thomas Jefferson University Research Magazine

While the clinicians of Jefferson Health were on the front lines of the battle with COVID-19— treating nearly 16,000 COVID patients and testing 35,000+ people—just behind them were the basic science researchers working hard to understand the molecular and cellular mechanisms driving the disease and the clinician-scientists working to adapt existing therapeutics to the unique challenges created by SARS-CoV-2.

Since early 2020, Jefferson researchers published more than 260 research studies on the coronavirus’s biology and on treatments

Covid’S Impact On Cancer Diagnosis

Thomas Jefferson University Research Magazine

While there are studies underway to characterize the direct effects of the COVID-19 pandemic on the care of patients with cancer, there have been relatively few quantitative reports of the impact that efforts to control the pandemic have had on the normal course of cancer diagnosis and treatment encounters. However, a multicenter research team led by Jack London, PhD, research professor emeritus of cancer biology, and Christopher McNair, PhD, associate director for data science at Sidney Kimmel Cancer Center and assistant professor of cancer biology, is studying that now. They have used encounter data from 20 healthcare institutions to compare …

Applied Solutions For Pandemic-Spurred Problems

Thomas Jefferson University Research Magazine

As a university with a large, comprehensive healthcare system, Jefferson has been on the front lines of the pandemic. The situation has required that everyone become a creative problem solver: faculty, staff and students have stepped up to analyze problems as they emerge and develop solutions for an array of issues. It has been a high-pressure demonstration of applied research and development in real time, and a potent example of how the University is spurring a convergence of disciplinary perspectives to address new and evolving challenges.

“Applied science uses in-depth inquiry to rigorously analyze problems and then develop and test …

Probing Molecular Mechanisms Of Viral-Host Interactions

Thomas Jefferson University Research Magazine

Holly Ramage, PhD, assistant professor of microbiology and immunology, is taking on some of the world’s most prevalent infectious diseases. She seeks to understand the molecular mechanisms of viral-host interactions in the flaviviruses—including dengue, Zika and West Nile virus—that are endemic in many areas of the world.

“Increasing evidence indicates that many viruses, including flaviviruses, have evolved mechanisms to manipulate cellular machinery in order to promote infection,” Dr. Ramage says. “My lab examines the physical interactions that occur between flavivirus and host-cell proteins. We use powerful proteomics and genomics techniques—including siRNA knockdowns, CRISPR knockouts and mutagenesis strategies—to identify the changes …

Striving To Understand Disparities In Cancer Care

Thomas Jefferson University Research Magazine

A key element of the mission of the Sidney Kimmel Cancer Center–Jefferson Health—and an objective of many researchers across the University—is to understand and mitigate the disparities in cancer incidence, treatment and outcome too often experienced by patients who are African American or Latinx, have low incomes or have limited access to care.

In the Philadelphia region, for example, prostate cancer incidence and mortality rates are significantly higher for African Americans than Caucasians, but the causes of this major disparity are unknown. Many researchers have believed that the difference in outcomes results from African American men’s poor clinical response to …