Fenghuang Zhan, M.D., is executive director of Myeloma Center Basic Research and the Morrison Family Endowed Chair at UAMS. He serves as a professor in the Department of Internal Medicine and is leader of the Genetics, Genomics and Proteomics faculty. His research is funded by competitive grants of over $3 million. He is a recipient of a $1.8 million grant from the Riney Foundation.

“The most important part of my contribution is to translate my research results into clinic usage to help improve myeloma care,” says Zhan.

Tells about your current research

I’m researching drug resistance and immune therapy in multiple myeloma (MM). The extreme variability in survival among patients with MM suggests that specific genetic lesions, possibly reflected in altered gene expression profile patterns in tumor cells, may account for the divergent clinical outcomes. My laboratory is interested in understanding how the genetic alterations in cancer cells contribute to tumor progression, alter treatment response, and create vulnerabilities that may be targeted therapeutically. Our previous work demonstrates that High NEK2 drives myeloma drug resistance and poor prognosis. Monotherapy with PD-1/PD-L1 inhibitors has shown disappointing results in MM, even though targeting immune checkpoints represents a new and very promising approach for the treatment of many solid tumors and certain types of hematologic malignancies. Is there any relationship between NEK2 and the disappointing results of targeting immune checkpoints in MM? To facilitate our research, we are combining genetic and genomic tools that enable us to explore various aspects of cancer biology in a comprehensive way. Current efforts strive to identify new components of NEK2 networks and characterize their impact on immune checkpoints blockade response. In addition, we are defining new biomarkers for targeting immune checkpoint therapy and developing new strategies for high risk (PR/relapsed) MM patients. 

Another research focus is on tumor-initiating cells (TICs) in MM. Although a universally accepted TIC phenotype has not yet been identified, the establishment of a TIC phenotype is critical if we want to fully understand the biology of these cells. Many studies indicate that CD24 has been recognized as a legitimate cancer stem cell marker in multiple cancers. Our studies demonstrated that CD24⁺ MM cells maintain the features of self-renewal and drug resistance in MM, providing a biomarker for myeloma genesis and targeted therapy. Myeloma tumor-initiating cells (MM-TICs), characterized by increased drug resistance and self-renewal capacity, are very likely responsible for our failure to cure myeloma in the majority of patients. Our goal is (1) To determine how the CD24⁺ primary MM cells (CD38⁺CD45^–) contribute to drug resistance; (2) To define TIC features; and (3) To develop MM TIC-targeted therapies in vitro and in vivo in a pre-clinical mouse model.  

Multiple Myeloma is virtually always preceded by a monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM), which are pre-malignant conditions and more prevalent in the elderly population. MGUS patients are not routinely screened since there is currently no treatment that has demonstrated efficacy in reducing the risk of progression of MGUS to MM. Taking advantage of our expertise in MGUS and MM biology and the area of genomics, with relevant mouse models in hand and availability of exceptional human MGUS resources, we are uniquely positioned to discover the key factors that are associated with MGUS progression. Then we are able to develop novel therapies based on a modulation of MGUS risk factors. 

What is your relationship to cancer?

My paternal grandmother is a breast cancer survivor, and my paternal grandfather passed away from colorectal cancer when I was a child. They were both cigarette smokers like many others in their poor, rural and underserved community. Growing up, I saw how my grandparents and other family members struggle to quit smoking and suffer from tobacco-related diseases. These experiences compelled me to become an epidemiologist dedicated to improving smoking cessation and combatting tobacco-related heath disparities among populations disproportionately burdened by tobacco.

What do you hope to contribute to the Cancer Institute? 

I hope to support the Winthrop P. Rockefeller Cancer Institute goal of achieving NCI designation by conducting and publishing innovative studies, developing community-based initiatives, and obtaining research funding. Tobacco use is a leading cause of cancer and cancer mortality, and smoking rates in Arkansas are higher than the national average. Through my research I seek to prevent and reduce tobacco use among Arkansans and inform tobacco control efforts at the national and state/local levels. I am excited to join the Cancer Institute as a public health professional and collaborate on cancer-related research to improve the health of Arkansans.

Tell us about your current research 

My current research focuses on the role of social-environmental and psychosocial factors as contributors to tobacco use and related disparities. My work often combines quantitative and qualitative epidemiologic methods. I aim to utilize my research to inform tobacco regulations and leverage technology-supported observational studies and interventions to increase successful smoking cessation among vulnerable and disadvantaged populations, such as African Americans and rural and low-income communities. 

I also completed predoctoral and postdoctoral fellowships with two NIDA/FDA funded Tobacco Centers of Regulatory Science (TCORS) and the Translational Addiction Research T32 program based in the UAMS Psychiatric Research Institute. My training informed my second line of research which focuses on tobacco regulatory science, a field of research specifically designed to inform real-time FDA regulation. My tobacco regulatory science studies aim to identify how risk perceptions and tobacco product characteristics (i.e., flavors, product type) influence tobacco use behaviors among disadvantaged populations.

I was recently awarded two pilot grants as PI, including one from the Arkansas Center for Health Disparities (ARCHD) in the UAMS College of Public Health. My mixed-methods pilot study investigates how perceived harmfulness of nicotine influences use of evidence-based and non-evidence based quit aids that contain nicotine (i.e., nicotine replacement therapy, e-cigarettes) among African American and White cigarette smokers aged 18-34. We aim to use findings from this study to inform future grant proposals and develop interventions to improve early age smoking cessation.

Associate Professor
Department of Biomedical Informatics
UAMS College of Medicine
Scientific Director, UAMS Genomics Facility

What is your relationship to cancer?

Growing up I was very close to my maternal grandfather, a retired New York City fireman and WWII veteran. He died from lung cancer when I was 15. He was a big person, 6’2” and 200 lbs. He was only 120 lbs. when he died.

I didn’t know how sick he was and that he was never going to get better. Every week, he seemed thinner and weaker, and I was often asking my mother why Papa was not getting better. I’ve kept his sons, also now retired New York City firefighters, informed of my lung cancer research.  We all still miss Papa.

What are your research goals? 

As a member of the Developmental Therapeutics Research Group, my research uses advanced molecular profiling to determine the role of the liquid biopsy in early stage cancer diagnosis. With the analysis of a simple blood test, we can find circulating tumor DNA (ctDNA), which are nucleic acid biomolecules shed by a tumor into the blood and detected by Next Generation Sequencing (NGS). Some of these tests are currently commercially available and FDA approved for patients with advanced (metastatic) disease. Now researchers are working to translate their foundational work into cutting-edge care for cancer patients at all stages of disease (and tumor types) and eventually for screening assays.

I began a clinical trial in 2019 to develop an advanced liquid biopsy method for diagnosing and monitoring lung cancer. Funded by a $1.47 million grant from the Food and Drug Administration (FDA), my lab tests lung tumor samples by running genetic sequencing and regrowing them using different methods. If the tumors are large enough, we test existing drugs and novel combinations of existing drugs on the tumors for the most effective treatment. This information is stored in a tumor bank so that doctors know the best treatment to use if the patient returns. We look for aggregate patterns on what treatments work best for different types of tumors.

In a related effort, I am part of an FDA-funded international collaboration whose recently published findings reveal that five commercially available assays can reliably detect circulating tumor DNA of late-stage and metastatic cancers.

Published April 12, 2021, in the journal Nature Biotechnology, the scientific study team includes researchers at the FDA’s National Center for Toxicological Research in Jefferson, Arkansas, and 12 participating laboratories in Europe, Australia, Asia and the United States.  Nature’s behind the paper channel  further explores aspects of how this research paper came to be and where subsequent research may lead.

What do you hope to contribute to cancer research and to the Cancer Institute?

As a medical oncologist, biomedical informaticist and computer engineer, I bring a unique combination of expertise that has served me well in the quest to make a simple blood test part of oncology clinical practice, along with advancing the personalized treatment of cancer.

ENHANCE: A randomized, double-blind, multicenter study comparing Magrolimab in combination with Azacitidine versus Azacitidine plus placebo in treatment-naïve patients with higher risk Myelodysplastic Syndrome

Principal Investigator: Muthu Veeraputhiran, M.D., MPH, FACP, Clinical Program Director, Stem Cell Transplantation and Cellular Therapy 

Sponsor: Gilead Sciences

Patients with intermediate, high and very high risk Myelodysplastic Syndrome (HR-MDS) have a median overall survival of 0.8 to 3.7 years. Despite the high unmet need in this patient population, Aazacitidine (AZA) is the only approved therapy for HR-MDS which has improved overall survival in clinical trials to date. Magrolimab is a first-in-class monoclonal antibody that blocks the macrophage inhibitory immune checkpoint CD47, a “do not eat me” signal overexpressed on tumor cells. Binding of Magrolimab to CD47 leads to phagocytosis of tumor cells. AZA increases expression of prophagocytic “eat me” signals, facilitating synergy with Magrolimab. In an ongoing phase 1b study, the combination of Magrolimab + AZA led to high response rates (ORR 91%, with a CR of 42%) and an acceptable safety profile without significant immune-related adverse events. 

This is a double-blind multicenter Phase 3 clinical trial with 1:1 randomization to AZA +/- Magrolimab to help treat intermediate and high risk MDS patients with an option of going to allogeneic transplant as decided by the treating hematologist. UAMS is the only center to have this trial option for MDS open in state of Arkansas. 

As a cancer survivor, Dr. Wolfe brings a passion to pancreatic cancer research that few others can. A recent recipient of a TRI Career Development Award, Wolfe is investigating the role of oncogenic KRAS in regulating the DNA repair of RAD18, an enzyme with a major role in pancreatic cancer DNA repair. 

What is your relationship to cancer? How did you become involved in cancer research?

My journey to becoming an oncology physician and cancer researcher has been ongoing for nearly 20 years. After a personal bout with cancer in high school, I decided early on that I wanted to dedicate my career (and life) to helping cancer patients. I discovered that I was both passionate about laboratory research and clinical care, so I earned a dual M.D./Ph.D. My current research focus is on discovering novel therapeutic strategies for the deadly disease of pancreatic cancer. In the lab, I use genetic and proteomic approaches to address the fundamental mechanisms of genetic alterations in cancer cells which result in heightened DNA repair leading to radiation and chemotherapy resistance. I was recently awarded the UAMS Translational Research Institute’s KL2 Mentored Career Development Award to investigate the mechanism underlying the role of oncogenic KRAS in regulating the nuclear DNA repair enzyme RAD18, a major promoter of DNA repair in pancreatic cancer.

What do you hope to contribute to the UAMS Cancer Institute?

It is an honor to be joining the UAMS Cancer Institute as a physician-scientist in Radiation Oncology. I believe that I will contribute to the overall goals of the Cancer Institute which include development of novel treatment strategies for the deadly disease of pancreatic cancer, provide compassionate and excellent care for our cancer patients, and perform and publish translational cancer research and obtain research funding. All of these contributions will help propel UAMS to our goal of NCI designation.

More about Adam Wolfe, M.D., Ph.D.

I joined the Winthrop P. Rockefeller Cancer Institute in July 2021 after completing my residency in Radiation Oncology at Ohio State University (OSU). There, I completed a Holman Fellowship researching DNA repair mechanisms of resistance in pancreatic and thyroid cancers. I was awarded research funding from both the Radiation Oncology Institute and the Radiological Society of North America during my fellowship at OSU. I received dual M.D. and Ph.D. degrees from the Medical Scientist Training Program at The University of Texas McGovern Medical School and MD Anderson Cancer Center Graduate School of Biomedical Sciences in 2016.

View Dr. Wolfe’s page on the Cancer Institute Research Directory 

Neuro-oncologist specializing in brain and spine cancer

Dr. Horta earned her medical degree at the University of Sao Paulo in Brazil, where she also served a residency in neurology and completed a clinical fellowship in neuro-immunology. She completed a fellowship in research at the Neuro-immunology Laboratory at the Mayo Clinic in Rochester, MN, and a clinical fellowship in neuro-oncology at Henry Ford Hospital in Detroit. Horta also served a residency in neurology at the University of Minnesota in Minneapolis. She joined UAMS in 2020 as a neuro-oncologist and has since built UAMS’ neuro-oncology practice. 

Q. What is your relationship to cancer?

A. I think neuro-oncology chose me. Going back to my first residency, I took care of many more patients that were in the neurology ward because a tumor was causing their symptoms. In my second residency, the cases that caught my attention were neuro-oncology ones. Also, people close to me had brain tumors, and this gives me another perspective.  

Q. When did you first become involved in cancer research?

A. I first got involved in cancer research in 2011 at the Mayo Clinic when I was working with paraneoplastic diseases that cause neurological problems because of cancer in the patient’s body. In the attempt to fight cancer, the immune system sometimes gets confused and starts to attach to the brain, spinal cord or the nerves of the patient.

Q. What do you hope to contribute to the Cancer Institute at UAMS?

A. I hope to contribute so much to the UAMS Cancer Institute. When I came to UAMS, we had to first build the neuro-oncology service. We are now bringing pharmacological clinical trials to patients with brain tumors at UAMS. We are also trying to better understand the impact on cognition that many cancers bring to patients, and how we can develop ways to identify and follow it. A brain tumor diagnosis can impact the patient and family so much, causing depression and anxiety that not only bring worse quality of life, but also impacts survival.  This is another topic of study; how can we detect those mood disorders and how can we act upon it.

I am also seeing patients with neurofibromatosis and tuberous sclerosis. Those diseases can cause tumors and cancer in many parts of the body, but mainly the brain, spinal cord and nerves. We are trying to develop a Neurofibromatosis Multidisciplinary Clinic and bring clinical trials for those patients. Also, brain tumors in patients with tuberous sclerosis can be treated with an FDA-approved oral medication, and we are bringing this option to our patients.

Researchers at the UAMS Winthrop P. Rockefeller Cancer Institute are doing their part fight COVID-19.

Deputy Director Alan Tackett, Ph.D., and Josh Kennedy, M.D., associate professor in the UAMS College of Medicine Department of Pediatrics Division of Allergy and Immunology, are leading a National Institutes of Health (NIH)-funded team to track virus variants circulating in Arkansas.

The $770,000 NIH grant is devoted to a strategic collaboration among researchers, faculty and clinicians at UAMS, Arkansas Children’s, Baptist Health and the Arkansas Department of Health. The Arkansas Sequencing (ArkSeq) Consortium, as it’s referred to, will be a source for COVID-19 samples from across the state to be used for sequencing virus variants.

“NIH has strategically allocated funds in key sites across the nation for COVID variant identification and tracking,” Tackett said. “Our research team was identified as the group in Arkansas to lead these important efforts. With the surge in delta variant infections in our state, we have redirected resources from cancer and other disease research towards virus sequencing to help our state identify and track current and future variants of concern in the adult and pediatric populations,” he said.

“The delta variant is rampant across the U.S. and Arkansas,” said Kennedy. “It currently represents more than 80% of the genomes sequenced from samples from our state. We need to be ready for what variant might be next, and this work will help us identify these new variants when they develop,” he said.

To date, Arkansas has uploaded just over 1,700 COVID-19 samples to national databases –a total of only 0.48% of all cases.  Tackett and Kennedy expect to yield seven times more sequences from Arkansas for national databases and produce additional samples for future study. The ArkSeq Consortium has already provided more than 2,000 samples that will be sequenced through Kennedy’s lab and the genomics cores at Arkansas Children’s Research Institute (ACRI).

“Sequencing for variants of SARS-CoV-2 will help us to understand the evolution of the virus over time, and it will help determine when or if the virus can evade our immune systems and cause greater disease,” Kennedy said.  “We hope to provide this level of detail to front-line health care workers in our state to help more people faster.”

Kennedy is overseeing viral sequencing at an NIH Center of Biomedical Research Excellence, directed by Tackett at ACRI. Data analysis is conducted at UAMS under the direction of Stephanie Byrum, Ph.D., associate professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology and director of the Winthrop P. Rockefeller Cancer Institute Bioinformatics Shared Resource, and David Ussery, Ph.D., professor in the UAMS College of Medicine Department of Biomedical Informatics. Bioinformatics will be performed in collaboration with the Arkansas INBRE program at UAMS.

This research is supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number P20GM121293.

Assistant Professor, Department of Biochemistry and Microbiology, UAMS College of Medicine, Member, Winthrop P. Rockefeller Cancer Institute

Q. What is your relationship to cancer? 

A. My research focuses on non-Receptor Tyrosine Kinase (nRTK) mediated TGFβ/SMAD signaling in tumorigenesis and metastasis, and aims to discover novel therapeutic mechanisms for treating triple negative breast cancer (TNBC). I am a member of the Epigenetics, Cancer, Systems Biology and Proteomics Group of the Winthrop P. Rockefeller Cancer Institute (WPRCI). It is an exciting research program that brings an array of expertise together to leverage our effort to defeat cancer. My lab will apply systems-biology approaches to quantitatively understand healthy and cancer cell signaling to develop new precision medicine therapies for improving metastatic TNBC patient survival and quality of life.

Q. What are you currently working on in the lab? 

A. The switch of anti-tumorigenic and anti-metastatic function of TGF-β/SMAD4 signaling to a metastatic- promoting factor remains a long-standing biological paradox in metastatic breast cancer. Recently, we showed that BRK, a non-receptor protein tyrosine kinase, promotes metastatic potential by phosphorylating SMAD4 in breast epithelial cells. The phosphorylated-SMAD4 promotes interactions with chromatin remodeling complexes. These chromatin remodelers are master epigenetic regulators that repress transcription and have been implicated in breast cancer pathogenesis. Currently, we are determining how phosphorylated-SMAD4 coordinates with epigenetic modifiers to reprogram gene expression in metastatic TNBC cells. We are also synthesizing a BRK-specific proteolysis targeting chimera (PROTAC) to deplete BRK to restore the anti-tumorigenic and anti-metastatic functions of the TGF-β/SMAD signaling to prevent TNBC metastasis.

Q. What do you hope to contribute to the Cancer Institute? 

A. I investigated the molecular mechanism of tumorigenesis and metastasis of breast cancer and I received advanced training on proteomics, chromatin biology and system biology during my postdoctoral training. I believe that mass-spec based proteomics is an essential tool for studying signal transduction pathways and it can provide molecular insight of complex biological processes. I am enthusiastic to collaborate and support other Cancer Institute members to apply proteomics in their research programs. I do believe our collaborative successes would be beneficial in our pursuit of NCI designation for the Winthrop P. Rockefeller Cancer Institute.

More about Sayem Miah, Ph.D.

I recently joined UAMS as an assistant professor in the Department of Biochemistry and Molecular Biology and am a member of the Winthrop P. Rockefeller Cancer Institute. I am very excited to be a member of this Cancer Institute and its long-standing reputation as a cancer care provider for the people of Arkansas. UAMS is an ideal place to translate basic research into translational research. My laboratory is studying the non-receptor tyrosine kinases (nRTKs) in order to restore anti-tumorigenic and anti-metastatic functions of the TGFβ/SMAD signaling to prevent TNBC metastasis. TNBC is particularly prone to aggressive metastases, for reasons that are still poorly understood. Protein kinase inhibitors are a major focus of the current oncology market and there are >35 FDA-approved options for drugs that target tyrosine kinases. This makes nRTKs a viable and promising target for tackling metastasis in TNBC. Intriguingly, the inhibition of the kinase activity of nRTKs did not always yield anticancer efficacy—suggesting an alternate kinase-independent role for nRTKs in tumorigenesis and metastasis. Thus, we are synthesizing a PROTAC to deplete nRTKs to restore the anti-tumorigenic and anti-metastatic functions of the TGFβ/SMAD signaling to prevent TNBC metastasis. I am collaborating with pharmaceutical chemist to synthesize BRK specific PROTAC and with an oncologist for a future investigator-initiated clinical trial. 

For this research, my laboratory will extensively use advanced proteomics, biochemical, genomic and molecular biology techniques to elucidate molecular mechanism of cancer metastasis. During my master’s degree training in Medical Biology at the University of Linkoping, I gained proficiency with an array of molecular biology techniques to study the underlying biology of disease. My interest in disease biology led me to pursue graduate work studying the role and mechanism of BRK in tumorigenesis. I carried out my doctoral training in the laboratory of Dr. Kiven E. Lukong at the University of Saskatchewan, Canada. 

During my postdoctoral training (Washburn Lab, Stowers Institute for Medical Research, Kansas City, MO), I combined my new and prior skills, and have carved out a unique interdisciplinary research program that has uncovered unprecedented opportunities to study BRK regulating TGF-β/SMAD signaling in metastatic breast cancer. I took a “systems-wide” interrogation approach for studying signaling networks using advanced chemical proteomic, biochemical, and genomic techniques to uncover molecular biology of tumorigenesis. I demonstrated that activated BRK directly interacts with and phosphorylates SMAD4 and causes proteasomal degradation to repress tumor suppressor gene FRK and to increase expression of the mesenchymal markers SNAIL and SLUG and published in Science Advance (https://pubmed.ncbi.nlm.nih.gov/31681835/). This research on BRK and TGF-β signaling that I conducted at Stowers led to my interest in synthesis of BRK-PROTAC to deplete BRK to tackle TNBC what I will pursue here at UAMS.