News

The effect of cardio-selective beta blocker on diastolic dysfunction in children with sickle cell disease.

Sickle cell disease in the new era: Advances in drug treatment

Patients with sickle cell disease who develop end-stage kidney disease continue to experience poor survival - A 19-year United States Renal Data System study.

Winer JC, Yee ME, Ataga KI, Lebensburger JD, Zahr RS. Br J Haematol. 2022 Oct 3. doi: 10.1111/bjh.18494. Online ahead of print. PMID: 36191963 No abstract available.

Dr. Marquita Nelson was listed in Memphis Magazine's 2022 “Top Doctors” list.

Dr. Ataga's article, "Longitudinal Study of Glomerular Hyperfiltration in Adults with Sickle Cell Anemia: A Multicenter Pooled Analysis" has been published online by ScienceDirect.

Kenneth Ataga, MD, Director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center (UTHSC), was recently awarded $3.2 million from the National Heart, Lung and Blood Institute for a project that enlists artificial intelligence in the fight against sickle cell disease. Santosh Saraf, MD, associate professor in the Department of Medicine at the University of Illinois at Chicago, is a co-PI on the grant. (Read More)

A recent paper from our group on machine learning and prediction of rapid kidney function decline in sickle cell anemia. (Read the latest publication)

One of the missions of the Department of Medicine is to foster and develop research.  In efforts to support research and the development of new extramural funding, the DOM has offered 2 Development Grants for this upcoming academic year for faculty in the Department of Medicine.   It is anticipated that this award will culminate in a new grant application by the end of the academic year.  We received many excellent applications for these awards that were peer reviewed by a committee.  I am pleased to announce that the following faculty were selected for funding this year:

Laila Elsherif, PhD
Assistant Professor of Medicine
Division of Hematology & Oncology
“Effect of PAI-1 Increase on Neutrophil Apoptosis Delay in Sickle Cell Disease”

Zhousheng Xiao, PhD
Associate Professor of Medicine
Division of Nephrology
“Novel Role of PC1/PC2 Complex in Adipocyte Metabolism”

Please help me in congratulating our Department of Medicine grant awardees!

This article was originally published on UTHSC News. You can view the original news article here.

Written by Lee Ferguson | August 4, 2020

A new research project that could impact and expand the discovery of new treatment options for sickle cell patients has received significant federal funding. The National Heart, Lung, and Blood Institute awarded nearly $1 million to Athena Starlard-Davenport, PhD, assistant professor of Genetics, Genomics, and Informatics in the UTHSC College of Medicine, for her project titled, “MicroRNA-based epigenetic approach to induce fetal hemoglobin.”

The grant, the first national award for Dr. Starlard-Davenport, is also a significant milestone for UTHSC’s Office of Research, as it puts the total external dollars generated from CORNET-funded work over the $20 million mark. The CORNET Awards are a seed funding program for interdisciplinary collaborations on new research.

“For the past 100 years, only four drugs have been approved by the FDA for the treatment of sickle cell disease,” Dr. Starlard-Davenport said. “Those patients need more treatment options depending on their symptoms and complications.”

Sickle cell disease is very common. One in 13 African Americans have the sickle cell trait and over 100,000 people in the U.S. have sickle cell disease. Individuals with sickle cell suffer from severe pain crises that increase their risk of organ failure and premature death. The sickle cell mutation causes production of abnormal sickle hemoglobin during the first year of life, when the body makes its switch from producing fetal hemoglobin (gamma globin) to adult beta globin. Fetal hemoglobin is normal in people with sickle cell disease; it is only the adult form of sickle hemoglobin that is abnormal. Scientists have found that reversing this normal switch, i.e. turning the gamma globin gene back on, counteracts symptoms, improves health outcomes and prolongs the lifespan of sickle cell patients.

To date, hydroxyurea is  the only FDA-approved drug with proven efficacy to do that. Though another class of epigenetic modulators − DNA methyltransferase (DNMT) inhibitors – has shown promise inducing fetal hemoglobin in sickle cell patients, they produce off-target side effects. Dr. Starlard-Davenport’s research is focused on a specific small molecule in this class, miRNA29b, for further study.

Dr. Starlard-Davenport has been investigating miRNA29b and fetal hemoglobin induction for four years. She got her start in 2016 with help from a new seed funding initiative launched that year by the UTHSC Office of Research, the CORNET Awards. She and her collaborator, Patricia Adams-Graves, PhD, professor of Medicine and hematologist at the Diggs-Kraus Sickle Cell Clinic at Regional One Health, won a CORNET in the Clinical Awards division for their project, “Investigation of miR29 as a novel fetal hemoglobin inducer and treatment for patients with sickle cell disease.”

“The CORNET award provided funding support to collect blood samples from sickle cell patients and to test whether our miRNA therapeutic could increase levels of fetal hemoglobin in vitro in cell culture and in preclinical sickle cell models. We did this work in collaboration with Betty Pace at Augusta University,” Dr. Starlard-Davenport said. Betty Pace, MD, is the Tedesco Distinguished Chair of Pediatric Hematology/Oncology at Augusta University. “The funding was used to purchase reagents for running the necessary biochemical assays, including our miRNA mimic, cell culture reagents.”

The CORNET program was begun by Steven Goodman, PhD, vice chancellor for Research, to encourage interdisciplinary collaboration on new research that will lead to larger, national grants. In the nearly four years since their inception, the awards have supported 52 new collaborative research teams and their groundbreaking initiatives. With this latest national award, external dollars generated from CORNET work has reached $20,604,972, an 11.6-fold return on a $1.78 million investment.

“This NIH award for studies to increase fetal hemoglobin expression thereby reducing sickle cell severity is important for many overlapping reasons,” Dr. Goodman said. “It is the first NIH award for Dr. Starlard-Davenport. We were able to assist Athena and her colleagues to obtain the preliminary data that led to the award through the CORNET award program. This extramural award put the CORNET program over the $20 million threshold in return on investment. Dr. Starlard-Davenport has been a mentee in the wonderful PRIDE program, which focuses on jump-starting the career of junior underrepresented minority faculty. The director of this PRIDE Program is Dr. Betty Pace who mentored Dr. Starlard-Davenport and is an investigator on the NIH Award. It is amazing how many stars aligned in this one NIH award to a very deserving new investigator. But most important is the impact that this study can have upon the quality of life of people around the globe who suffer from this genetic disease.”

“In the initial CORNET application, my team provided preliminary results to show that miRNA29b could increase levels of fetal hemoglobin in a compatible human cell line, but we needed further preliminary data to determine what effect miRNA29b had on fetal hemoglobin induction in red blood cells from individuals with and without sickle cell disease,” Dr. Starlard-Davenport said. The NIH funding she just received, $928,317 to be distributed over three years, will allow her team to collect blood samples from sickle cell patients and test whether this molecule increases the expression of fetal hemoglobin that blocks sickle hemoglobin polymerization and improves clinical symptoms. The long-term goal is to develop miRNA29b as a new drug for treating patients with sickle cell.

Dr. Starlard-Davenport is the principal investigator on a team of clinicians and scientists that includes, in addition to Dr. Adams-Graves and Dr. Pace, Ken Ataga, MD, director of the UTHSC Center for Sickle Cell Disease; Daniel Johnson, PhD, director of the UTHSC Molecular Bioinformatics Center; and Biaouri Li, MD, professor in the department of Pediatric Hematology/Oncology at Augusta University.

This article was originally published on UTHSC News. You can view the original news article here.

View a video recording of the 2019 Norfleet Forum at the following links. Part 1 | Part 2

Clinicians and researchers from around the country gathered in Memphis Friday for the 2019 Frank M. Norfleet Forum for the Advancement of Health to discuss sickle cell disease research and treatment. They looked back at how the disease has developed over the last century and what the future holds for those born with it and those who are trying to cure it.

Themed “More than 100 years of Sickle Cell Disease: Development of Novel Therapies,” the daylong conference at the National Civil Rights Museum was organized and led by Kenneth Ataga, MD, director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center and the Memphis Consortium for Sickle Cell Disease and Non-Malignant Hematology Research. Dr. Ataga joined UTHSC in 2018 and is recognized nationally and internationally as an expert clinician and researcher in the field of sickle cell disease.

Progress has been made in diagnosing and treating sickle cell disease, the panelists said.

Improvements in drug therapies, screening for the disease at birth, better supportive care, developing gene therapy, and ongoing research have improved outcomes for those with the disease.

“A lot of work still has to be done,” Dr. Ataga told the group.

He said it is necessary to improve access to comprehensive care by specialists, increase advocacy for those with the disease, improve the infrastructure for clinical trials, and promote drug discovery and testing of novel compounds to treat the disease.

Health disparities, including poverty and lack of access, prevent many patients around the world from getting the care that could improve their quality of life.

Panelists included researchers from Boston Children’s Hospital, Albert Einstein College of Medicine, Duke Comprehensive Sickle Cell Center, St. Jude Children’s Research Hospital, Cincinnati Children’s Hospital, and Vanderbilt University.

The first Norfleet Forum was held in 1980 at UTHSC. The annual conference was created to focus on the improvement of health in the community, the state, and around the world through discussion of health policies and developments. It was funded by a gift to the university in honor of Memphis businessman Frank M. Norfleet through the Community Foundation of Greater Memphis. Other recent topics have included kidney disease in the African American community, childhood obesity, and alcohol use disorders.

Jon McCullers, MD, chair of pediatrics at UTHSC and pediatrician in chief at Le Bonheur Children’s Hospital, said the Norfleet Forum allows the university to improve scientific and community knowledge on relevant health care issues and to foster collaboration among researchers that could result in moving science forward.

“Norfleet allows us to bring in 10 or 15 outside speakers, which is a tremendous thing that you don’t see at a local or regional conference,” he said. “It’s unique and it’s very much appreciated. “

FOX13 Memphis – Story by Kody Leibowitz, July 9, 2019

The University of Tennessee Health Science Center College of Medicine's Executive Dean Scott Strome announced the award of internal funds to four projects in the College of Medicine at Memphis. 

For the Collaborative Intramural Research in the College of Medicine (CIRCA) support program the following were selected for funding:

The Association of Podocyturia with Progressive Glomerular Injury in Sickle Cell Disease

o   Kenneth I. Ataga, MD, Plough Foundation Endowed Chair & Professor of Medicine and Pediatrics

o   Adebowale Adebiyi, PhD, Associate Professor, Department of Physiology 

The goal of the CIRCA program is to stimulate innovative, interdisciplinary, team research leading to submission of an R01-scale grant application.  Specifically, CIRCA is designed to fund innovative research collaborations between a clinician (patient care responsibilities and/or a clinical researcher) and basic researcher in different departments. Matthew Ennis, PhD, Chair of the CIRCA proposal review committee noted “There were many meritorious applications and the decision to fund 2 proposals was an excellent choice based on thorough review by a committee with broad research expertise."

This article was originally published on UTHSC News. You can view the original news article here.

Written by Sarah Ashley Bloch | June 26, 2019

Newly published results from a multinational study co-authored by Kenneth Ataga, MD, director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center (UTHSC) and the Memphis Consortium for Sickle Cell Disease and Non-Malignant Hematology Research, indicated voxelotor, a novel experimental drug for sickle cell disease, reduced anemia and boosted the health of red blood cells in patients. Dr. Ataga is also the Methodist Endowed Chair in Sickle Cell Anemia at Methodist Le Bonheur Healthcare.

Sickle cell disease is an inherited blood disorder that affects red blood cells. It is caused by a genetic mutation in hemoglobin, resulting in the formation of abnormal hemoglobin known as sickle hemoglobin (HbS). Deoxygenation and the sickling of red blood cells can lead to chronic anemia and hemolysis, and ultimately result in multiorgan damage, stroke, and premature death. More than 100,000 Americans are affected by sickle cell disease, and Memphis has one of the largest populations for adult sickle cell disease in the country. There are only two U.S. Food and Drug Administration-approved treatment options currently available.

“With the limited drug therapies available for patients with sickle cell disease, the findings of this trial are quite exciting,” said Dr. Ataga, who also serves as the Plough Foundation Endowed Chair in Sickle Cell Disease. “With the complex nature of sickle cell disease, the development of drugs that have different mechanisms of action offers an opportunity for combination drug therapy and for individualized therapy based on the presence of specific disease-related complications.”

The Biopharmaceutical company Global Blood Therapeutics, Inc. aims to bring voxelotor to the market as a third treatment option.

Designed to evaluate the efficacy and safety of voxelotor, the phase 3 Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization (HOPE) Study enrolled 274 patients, ages 12 to 65, with sickle cell disease, from 60 institutions across 12 countries. The patients were divided into three trial groups that received either a 900-mg or 1,500-mg daily dose of voxelotor or a placebo. Clinical assessments were performed at various time points throughout the trial.

The study found that 51 percent of the participants who were administered the higher dose of voxelotor experienced a significant increase in hemoglobin levels after six months of treatment compared to seven percent in the placebo group. In addition, voxelotor treatment reduced the incidence of worsening anemia and the amount of hemolysis. Voxelotor was also deemed safe and well-tolerated by participants.

“While voxelotor improved anemia in the study patients, more studies are required to show whether there are also improvements in other sickle cell disease-related complications,” Dr. Ataga said.

Longer-term follow-up studies are being planned to assess voxelotor’s effects on vaso-occlusive crisis (or sickle cell crisis), morbidity, and mortality in sickle cell patients.

The HOPE Study results were recently published in The New England Journal of Medicine and presented at the European Hematology Association 24^th Congress in Amsterdam.