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.