The Wire

  • New tunnel, premium RV section at Talladega Superspeedway on schedule despite weather


    Construction of a new oversized vehicle tunnel and premium RV infield parking section at Talladega Superspeedway is still on schedule to be completed in time for the April NASCAR race, despite large amounts of rainfall and unusual groundwater conditions underneath the track.

    Track Chairman Grant Lynch, during a news conference Wednesday at the track, said he’s amazed the general contractor, Taylor Corporation of Oxford, has been able to keep the project on schedule.

    “The amount of water they have pumped out of that and the extra engineering they did from the original design, basically to keep that tunnel from floating up out of the earth, was remarkable,” Lynch said.

  • Alabama workers built 1.6M engines in 2018 to add auto horsepower


    Alabama’s auto workers built nearly 1.6 million engines last year, as the state industry continues to carve out a place in global markets with innovative, high-performance parts, systems and finished vehicles.

    Last year also saw major new developments in engine manufacturing among the state’s key players, and more advanced infrastructure is on the way in the coming year.

    Hyundai expects to complete a key addition to its engine operations in Montgomery during the first half of 2019, while Honda continues to reap the benefits of a cutting-edge Alabama engine line installed several years ago.

  • Groundbreaking on Alabama’s newest aerospace plant made possible through key partnerships


    Political and business leaders gathered for a groundbreaking at Alabama’s newest aerospace plant gave credit to the formation of the many key partnerships that made it possible.

    Governor Kay Ivey and several other federal, state and local officials attended the event which celebrated the construction of rocket engine builder Blue Origin’s facility in Huntsville.

6 months ago

Sustained cellular immune dysregulation in individuals recovering from COVID-19

(Pixabay, YHN)

COVID-19, which has killed 1.7 million people worldwide, does not follow a uniform path.

Many infected patients remain asymptomatic or have mild symptoms. Others, especially those with comorbidities, can develop severe clinical disease with atypical pneumonia and multiple system organ failure.

Since the first cases were reported in December 2019, the SARS-CoV-2 virus that causes COVID-19 has surged into a pandemic, with cases and deaths still mounting. Ongoing observational clinical research has become a priority to better understand how this previously unknown virus acts, and findings from this research can better inform treatment and vaccine design.

University of Alabama at Birmingham researchers, led by first-author Jacob “Jake” Files and co-senior authors Nathan Erdmann, M.D., Ph.D., and Paul Goepfert, M.D., have now reported their observational study, “Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection,” published in the Journal of Clinical Investigation.


In a commentary on the UAB study, published in the same issue, Phillip Mudd, M.D., Ph.D., and Kenneth Remy, M.D., both of Washington University, wrote, “The importance of these studies to provide context for the interpretation of immune responses generated by participants in COVID-19 vaccine trials, including how those responses change over time, cannot be over-emphasized. This information will be key in potential modifications to existing COVID-19 vaccines and treatments.”

The UAB researchers obtained blood samples and clinical data from 46 hospitalized COVID-19 patients and 39 non-hospitalized individuals who had recovered from confirmed COVID-19 infection. Both groups were compared to healthy, COVID-19-negative controls. Importantly, most individuals in the hospitalized group had active SAR-CoV-2 viruses in their blood and were in the hospital at the time of sample collection. All individuals in the non-hospitalized group were convalescent at the time of sample collection.

From the blood samples, researchers were able to separate specific immune cell subsets and analyze cell surface markers. From this complex information, immunologists can analyze how each individual’s immune system is responding during infection and during convalescence. Some of these results can reveal whether immune cells have become activated and exhausted by the infection. Exhausted immune cells may increase susceptibility to a secondary infection or hamper development of protective immunity to COVID-19.

In addition, the researchers were able to analyze changes over time, in two ways. The first was observing changes in surface markers over time, defined as days since the onset of symptoms for non-hospitalized samples. The second was directly comparing the frequencies of these markers between the first and second clinic visits for non-hospitalized patients who had blood samples collected at two sequential timepoints.

The most surprising finding involved non-hospitalized patients. While the UAB researchers saw upregulated activation markers in hospitalized patients, they also found several activation and exhaustion markers were expressed at higher frequencies in non-hospitalized convalescent samples.

Looking at these markers over time, it was apparent that immune dysregulation in the non-hospitalized individuals did not quickly resolve. Furthermore, the dysregulation of T cell activation and exhaustion markers in the non-hospitalized cohort was more pronounced in the elderly. “To our knowledge,” the researchers reported, “this is the first description of sustained immune dysregulation due to COVID-19 in a large group of non-hospitalized convalescent patients.”

For details of the comprehensive look at immune cells subsets during and after COVID-19 infection in hospitalized and non-hospitalized people, see the study, which includes an in-depth characterization of the activation and exhaustion phenotype of CD4+ T cells, CD8+ T cells and B cells.

The B and T cells from both patient cohorts had phenotypes consistent with activation and cellular exhaustion throughout the first two months of infection. And in the non-hospitalized individuals, the activation markers and cellular exhaustion increased over time. “These findings,” Mudd and Remy said in their commentary, “illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer-term effects that may shape the maintenance of immunity to SARS-CoV-2.”

A question now being explored, the UAB researchers say, is whether these observed immunologic changes are associated with symptoms experienced well beyond the acute infection, often described as “Long COVID.”

Co-authors with Files, Erdmann and Goepfert in the Journal of Clinical Investigation report are Sushma Boppana, Mildred D. Perez, Sanghita Sarkar, Kelsey E. Lowman, Kai Qin, Sarah Sterrett, Eric Carlin, Anju Bansal, Steffanie Sabbaj, Olaf Kutsch and James Kobie, Division of Infectious Diseases, UAB Department of Medicine; and Dustin M. Long, Department of Biostatistics, UAB School of Public Health.

Files is a graduate student in the UAB M.D.-Ph.D., Medical Scientist Training Program. Erdmann and Goepfert are assistant professor and professor, respectively, in the UAB Division of Infectious Diseases.

At UAB, Goepfert holds the Edward W. Hook, III, M.D., Endowed Professorship in Infectious Diseases.

(Courtesy of the University of Alabama at Birmingham)

9 months ago

Alabama clinical trial to test possible COVID-19 treatment for outpatients


Why is the COVID-19 virus more dangerous in people with existing illnesses?

Sadis Matalon, of the University of Alabama at Birmingham, and colleagues in Texas and San Francisco asked that question in a hypothesis paper published online in Physiological Reviews on March 27. They reviewed, in detail, research literature for hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease and kidney dysfunction, as well as many viral studies, studies of COVID-19 pathology and clinical presentation, and literature on the life-threatening acute respiratory distress syndrome.


Twelve days later, UAB Professor Emeritus Timothy Ness posted plans on for an exploratory COVID-19 outpatient study to test Matalon’s hypothesis and prevent worse clinical outcomes. His quick reaction is another example of how nimble UAB researchers have been during the COVID-19 pandemic.

In the Physiological Reviews paper, the researchers noted that all those comorbidities feature elevated levels of the extracellular protease plasmin. Plasmin is able to nick proteins at amino acid sequences called furin sites. For many viruses, this nicking increases their infectivity. Both SARS and MERS – the two virulent coronaviruses that are related to the COVID-19 virus – “have evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population,” the researchers wrote.

They noted that the COVID-19 virus, SARS-CoV-2, has a furin site on its spike protein, the vital protein for viral attachment to a lung cell. The researchers proposed that plasmin may cleave that site in the spike protein to increase its infectivity and virulence, and they hypothesized that, “the plasmin system may prove a promising therapeutic target for combating COVID-19.”

Ness already knew there is an inexpensive, commonly used drug – tranexamic acid, or TXA – that targets plasmin by inhibiting its conversion from the inactive precursor, plasminogen, to the active protease, plasmin.

TXA is approved by the U.S. Food and Drug Administration for treatment of heavy menstrual bleeding because having lower plasmin levels allows better clotting. TXA has a long track record of safety and is commonly given off-label. At UAB Hospital, TXA is used as a standard of care for orthopedic and cardiac bypass surgeries; it is commonly used for hemorrhaging trauma patients and has been used for spinal surgery, neurosurgery and corrective jaw surgeries. It is being studied for use in cesarean section surgeries.

For the clinical trial, Ness and colleagues have started a double-blind study, giving either TXA or a placebo pill to COVID-19 outpatients who were recently diagnosed. Patients also receive an anticoagulant. The overall goal of the exploratory study is to assess the safety and efficacy of five days of TXA versus placebo. Enrollment is ongoing.

Ness and colleagues hypothesize that the TXA treatment will reduce the infectivity and virulence of the virus, as measured by reduced need for hospitalization within a week if a patient’s condition deteriorates. Adults 19 years old and older are eligible, and all patients – whether in the control group or the TXA group – receive standard care as directed by their primary caretakers.

To learn more about the study, “TXA and Corona Virus 2019 (COVID19) in Outpatients,” patients and physicians can contact Dr. Timothy Ness at Patients who have recently tested positive for COVID-19 can call 205-934-6777 to see if they qualify for the study.

Other principal investigators for the trial are Dr. Sonya Heath, professor in the UAB Department of Medicine Division of Infectious Diseases; Dr. Brant Wagener, associate professor and Sadis Matalon, distinguished professor, both in the UAB Department of Anesthesiology and Perioperative Medicine. Ness is professor emeritus in that department.

Authors of the Physiological Reviews paper, “Elevated plasmin(ogen) as a common risk factor for COVID-19 susceptibility,” are Hong-Long Ji and Runzhen Zhao, University of Texas Health Science Centre at Tyler; Michael A. Matthay, University of California, San Francisco; and Matalon.

Matalon said the paper has been widely noticed. “Since its publication online, it has been downloaded 26,565 times and cited 55 times,” he said.

At UAB, Matalon holds the Dr. Alice McNeal Endowed Chair in Anesthesiology, and he is a Distinguished Professor and vice chair for Research.

(Courtesy of Alabama NewsCenter)

11 months ago

UAB launches second round of urgent, high-impact COVID-19 research

(UAB/Contributed, YHN)

Urgent high-impact COVID-19 research at the University of Alabama at Birmingham is catching its second breath, thanks to the generosity of Alabama business leader donors and the discovery and clinical skills of UAB researchers.

Ten new pilot projects — funded by $402,000 in donations — began Aug. 1. The projects will last six months and were selected for their high probability of having an impact on the COVID-19 crisis within weeks or months. Competition for funding was open to the entire university, and 76 applications were received, showing the intense interest of faculty across the campus.

This round of research grants follows 14 projects advertised to faculty of the UAB School of Medicine that were funded beginning May 1, after the Birmingham and Montgomery business community raised $1.1 million in just 20 days in March and April. Part of that money is helping fund this second round.


The pilot projects will yield payoffs down the road from the knowledge UAB researchers gain. Preliminary data from the pilots will form the basis for new grants and contracts, including pursuit of the $2 billion COVID-19 grant support being offered by the National Institutes of Health.

“The number of high-quality proposals we received made the decision on which ones we could fund very difficult,” said Kent Keyser, Ph.D., associate vice president in the Office of Research, who managed the second round and led the review process. “These projects, together with the 14 projects funded in May by the UAB School of Medicine, show once again that UAB is at the forefront in fighting COVID-19. We are grateful for the philanthropic support that made the program possible.”

The 10 projects have 27 principal investigators or co-investigators, and they come from a broad swath of the UAB School of Medicine, as well as an investigator from the UAB School of Public Health, Department of Epidemiology.

The School of Medicine departments represented by these investigators include:

  • The Department of Medicine and its divisions of Pulmonary, Allergy and Critical Care Medicine; Gerontology and Geriatric Medicine; Infectious Diseases; Gastroenterology; Preventive Medicine; and General Internal Medicine.
  • The Department of Pediatrics and its divisions of Pediatric Rheumatology, and Pediatric Pulmonary and Sleep Medicine.
  • The departments of Anesthesiology and Perioperative Medicine; Radiology; Cell, Developmental and Integrative Biology; Microbiology; and Pathology.

The interactions of investigators from all these backgrounds fulfill part of UAB’s strategic plan, Forging the Future, with the objective of enhancing UAB’s institutional culture of collaboration and innovation.

The titles of the funded grants also show the diverse research at UAB:

  • Clonal diversity of human antibodies to SARS-CoV-2 S-protein.
  • Glucocorticoid treatment of COVID-19 cytokine storm syndrome.
  • Therapeutics targeting COVID-19 entry into pulmonary epithelial cells.
  • Immunotyping COVID-related acute respiratory distress syndrome.
  • Circulating microbiota and microbial endotoxin drive uncontrolled immune activation of blood monocytes in COVID-19.
  • Development of a tri-specific neutralizing antibody for the treatment of SARS-CoV-2 infection.
  • Individual- and area-level risk factors for COVID-19 disparities in the Deep South.
  • Exploratory study of the effect of tranexamic acid treatment on the progression of COVID-19 in outpatients.
  • Molecular mechanisms underlying the pathogenesis of acute respiratory distress syndrome in critically ill SARS-CoV-2-infected patients.
  • Neutrophils as a driving mechanism of acute respiratory distress syndrome and death in COVID-19 patients.

“We are deeply grateful to our local and national philanthropic partners for quickly responding with critical support needed to accelerate UAB’s COVID-19 research efforts,” said Jessica Towns, UAB School of Medicine’s executive director of Development. “Through our recent Day of Caring and ongoing fundraising initiatives, we have seen tremendous generosity from the community. This support provides significant resources and encouragement to our scientists, faculty, staff and students during this challenging time.”

Although the first round of pilots was advertised to the School of Medicine, the projects included funding for Sue Feldman, R.N., Ph.D., in the UAB School of Health Professions, to ensure scalability of the UAB website to broader communities, including translating the site into Spanish. is a geographical symptom tracker, driven by crowdsourced, consumer-generated data to monitor and visualize COVID-19 symptoms across the United States with a focus on hard-to-reach communities in Alabama. also provides valuable research data for use by researchers across the entire UAB campus. is the precursor to Healthcheck, which is part of the GuideSafeTM platform of tools being used for returning to campus operations.

(Courtesy of UAB)

11 months ago

Altimmune COVID-19 vaccine candidate tested at UAB shows positive preclinical results

(UAB/Contributed, YHN)

Altimmune, Inc., a clinical-stage biopharmaceutical company, has announced positive results from the preclinical studies conducted in mice at the University of Alabama at Birmingham of its intranasal COVID-19 vaccine candidate, AdCOVID.

The studies — a collaboration between UAB and the Gaithersburg, Maryland-based Altimmune — showed strong serum neutralizing activity and potent mucosal IgA immunity in the respiratory tract. The induction of IgA antibody in the respiratory tract may be necessary to block both infection and transmission of the virus to prevent further spread of COVID-19. Based on these findings, AdCOVID is expected to be advanced to a Phase 1 safety and immunogenicity study in Q4 of this year. 


AdCOVID is designed to express the receptor binding domain of the SARS-CoV-2 virus spike protein, a key immune target that is essential for the virus to bind to cells and initiate infection. By focusing the immune response to this portion of the viral spike protein, AdCOVID elicited a strong systemic antibody response against the receptor binding domain in mice, achieving serum IgG antibody concentrations greater than 800 micrograms per milliliter just 14 days after administration of a single intranasal dose. In addition, AdCOVID stimulated serum viral neutralization titers of 1:320 by Day 28, two-times higher than the titer recommended by the U.S. Food and Drug Administration for investigational convalescent plasma as a treatment for severe COVID-19.

In a separate study with UAB, a single intranasal dose of AdCOVID stimulated a 29-fold induction of mucosal IgA in bronchoalveolar fluid of vaccinated mice. This level of IgA antibody stimulation is well above that associated with protection from disease in clinical studies of other mucosal vaccines. Frances Lund, Ph.D., lead UAB investigator for preclinical testing of the AdCOVID vaccine candidates, said, “The potent stimulation of mucosal IgA immunity in the respiratory tract may be crucial to effectively block infection and transmission of the SARS-CoV-2 virus, given that the nasal cavity is a key point of entry and replication for the SARS-CoV-2 virus.”

“Stimulation of immunity at this level just 14 days after a single dose is impressive for any vaccine, and is particularly notable for a potential coronavirus vaccine,” said Lund, the Charles H. McCauley Professor and chair of the UAB Department of Microbiology. The Lund lab did the preclinical testing in collaboration with the labs of Troy Randall, Ph.D., professor of medicine in the UAB Division of Clinical Immunology and Rheumatology; Kevin Harrod, Ph.D., professor in the UAB Department of Anesthesiology and Perioperative Medicine; and three more UAB Department of Microbiology labs led by Rodney King, Ph.D., assistant professor, Todd Green, Ph.D., associate professor, and John Kearney, Ph.D., professor.

In other details from the collaborative preclinical work, Altimmune announced that the antibody responses were accompanied by a rapid recruitment of CD8+ T cells, CD4+ T cells, dendritic cells and natural killer cells in the respiratory tract. Increases in both germinal center and memory B cells, as well as T follicular helper cells, all associated in prior vaccine development research with the generation of long-lived antibody responses, were observed in regional lymph nodes and the spleen

Preclinical data for the antigen-specific T cell response are expected in coming weeks, along with additional immunogenicity readouts.

The Altimmune–UAB collaboration was announced March 30, and Lund made that work the highest priority for her group. “The goal,” she said in March, “is to get the data to Altimmune as rapidly as possible, so they will use the information gained from the preclinical study to design their clinical trial in people.

Intranasal dosing provides AdCOVID with the potential to be administered rapidly and without the need for needles, syringes or trained healthcare personnel. In addition, AdCOVID’s expected room temperature stability profile may allow for broad distribution of the vaccine without the need for expensive cold-chain logistics, such as refrigeration or freezing.

UAB has extensive experience in conducting clinical studies of vaccines and has participated in studies sponsored by the Vaccine Evaluation and Trial Unit, part of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

At UAB, Randall holds the William J. Koopman Endowed Professorship in Rheumatology and Immunology, Harrod holds the Benjamin Monroe Carraway, M.D., Endowed Chair in Anesthesiology, and Kearney holds the Endowed Professorship in Immunology.

(Courtesy of UAB)

1 year ago

Search for drugs effective against COVID-19 includes UAB and Southern Research

(UAB/Contributed, YHN)

The University of Alabama at Birmingham will join an international effort coordinated by Scripps Research to test drugs for COVID-19.

The work centers around ReFRAME, a vast collection of drugs developed for other diseases that are already known to be safe for humans. Researchers at Calibr, the drug development division of Scripps Research, are teaming up with scientists from the United States, Europe and Asia to screen this vast collection for individual drugs or combinations that may be effective in treating people exposed to COVID-19.

Rich Whitley, M.D., distinguished professor of pediatrics, will lead the UAB effort.


“We will screen the Scripps Calibr repurposed library of compounds to determine if any licensed drugs have activity against Sars-Cov-2, the virus that causes COVID-19,” Whitley said. “If there are any that are active, we will plug them into my National Institutes of Health U19 grant and, specifically, the coronavirus project.”

In 2019, Whitley’s Antiviral Drug Discovery and Development Center at UAB was awarded a five-year, $37.5 million grant from the National Institute of Allergy and Infectious Diseases Centers of Excellence for Translational Research to study and develop treatments for high-priority infections. These include the coronaviruses that caused SARS and MERS, with the addition now of the novel coronavirus that causes COVID-19. The antiviral drug center is also seeking treatments for influenza viruses; flaviviruses like dengue, West Nile virus and Zika; and alphaviruses, such as Venezuelan equine encephalitis virus and chikungunya. Remdesivir, an investigational drug developed by Whitley for MERS and now produced by Gilead Sciences, is currently being tested in hospitals for treating COVID-19 patients.

In Birmingham, the screening of the ReFRAME compounds will be done at Southern Research’s state-of-the-art High-Throughput Screening Center, which has advanced robotic equipment and a well-trained staff with the capacity to run a wide variety of assay types.

Southern Research is a nonprofit scientific research organization, and its board is chaired by UAB President Ray Watts, M.D.

Compounds that show activity in the Southern Research screening would then be further tested by Whitley’s collaborators on the NIH U19 grant. Mark Denison, M.D., professor of pediatrics at Vanderbilt University Medical Center, would study a compound’s medicinal chemistry and mechanism of action. Ralph Baric, Ph.D., professor of microbiology and immunology at the University of North Carolina-Chapel Hill, would study preclinical cellular and animal models.

“COVID-19 is an unprecedented public health crisis that will only be brought fully under control by effective medical therapies,” said Peter Schultz, Ph.D., president and CEO of Scripps Research, La Jolla, California. “Repurposing drugs that have already been approved for use in humans, or compounds for which we have ample safety data, offers the most rapid path to finding an antiviral drug or drug combination that is effective against COVID-19.”

Shortly after the initial COVID-19 outbreak began in China, Calibr began sharing the ReFRAME library and conducting joint experiments with other research teams at Scripps Research and collaborating institutions worldwide. Support comes from the Bill & Melinda Gates Foundation.

“In the case of COVID-19,” said Arnab Chatterjee, vice president of Medicinal Chemistry at Calibr, “we could leverage this important resource, along with Calibr’s expertise in drug development and discovery, to collaborate with some of the world’s leading virology labs and quickly identify potential medicines.”

Schultz says that, while the results of the collaborations are still preliminary and need to be confirmed, they have already identified a number of compounds that show varying degrees of activity against the virus. The researchers hope to soon begin testing the drugs in cellular and animal models, including testing combinations of drugs that work by two different mechanisms for enhanced effectiveness.

At UAB, Whitley holds the Loeb Eminent Scholar Chair in Pediatrics.

(Courtesy of UAB)

1 year ago

UAB will test a COVID-19 vaccine candidate created by Altimmune Inc.

(UAB/Contributed, YHN)

The University of Alabama at Birmingham is launching a collaboration with the biopharmaceutical company Altimmune, Inc. for preclinical testing of a potential vaccine to prevent COVID-19 disease.

The testing at UAB will investigate immune responses to the vaccine in mice — a key step before the Gaithersburg, Maryland-based Altimmune can launch a Phase 1 human safety and immunogenicity trial in patients in Q3 of this year. The COVID-19 vaccine, called AdCOVID, is a single-dose vaccine candidate that is delivered by an intranasal spray.

Altimmune created AdCOVID in response to the COVID-19 global pandemic. The company has significant experience in the development of intranasal vaccine candidates for respiratory pathogens, including a seasonal and pandemic influenza vaccine and a vaccine for inhalation anthrax. The anthrax vaccine candidate is being developed under a $133.7 million contract with the U.S. Biomedical Advanced Research and Development Authority.


“We are eager to collaborate with Altimmune on this important project,” said Frances E. Lund, the Charles H. McCauley Professor and Chair for the UAB Department of Microbiology. “The expertise and infrastructure at UAB will be invaluable to the rapid progression of this vaccine into clinical studies,” she added.

Six UAB labs will work together on this urgent collaboration with Altimmune. “This project will be our highest priority for the group in the next few months as the goal is to get the data to Altimmune as rapidly as possible, so that they will use the information gained from the preclinical study to design their clinical trial in people,” Lund said.

In addition to Lund’s lab, the labs are led by Troy Randall, Ph.D., professor of medicine in the UAB Division of Clinical Immunology and Rheumatology; Kevin Harrod, Ph.D., professor in the UABDepartment of Anesthesiology and Perioperative Medicine; and three more UAB Department of Microbiology labs led by Rodney King, Ph.D., assistant professor, Todd Green, Ph.D., associate professor, and John Kearney, Ph.D., professor.

“It is critical that the biotechnology industry and academic institutions work together to prevent the further spread of COVID-19, and UAB is an ideal partner to support us in this effort,” said Vipin K. Garg, Ph.D., president and chief executive officer of Altimmune. “UAB has an impressive track record of cutting-edge research in virology and immunology, as well as in the clinical development of vaccines. In fact, Altimmune was founded through a technology license from UAB in 1997. We are excited to collaborate with UAB in our efforts, and we look forward to addressing this crisis together.”

UAB also has extensive experience in conducting clinical studies of vaccines and has participated in studies sponsored by the Vaccine Evaluation and Trial Unit, part of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Altimmune expects that the COVID-19 vaccine candidate will activate mucosal and cellular immune responses, as well as a strong antibody response in the blood, as was found for its influenza vaccine candidate, which uses the same proprietary intranasal vaccine technology. If the AdCOVID vaccine candidate is as stable as Altimmune’s influenza and anthrax vaccines candidates, that may allow inexpensive and efficient distribution of the millions of doses needed for widespread vaccination of populations.

At UAB, Randall holds the William J. Koopman Endowed Professorship in Rheumatology and Immunology, Harrod holds the Benjamin Monroe Carraway, M.D., Endowed Chair in Anesthesiology and Kearney holds the Endowed Professorship in Immunology.

(Courtesy of UAB)

2 years ago

UAB doctors find biomarker of early beta cell death before onset of Type 1 diabetes

(Jeff Hansen/UAB)

Beta cells in the pancreas produce insulin. Their death is a key feature of Type 1 diabetes, and that loss starts long before diagnosis. However, there has been no straightforward way to measure that early loss.

Anath Shalev, M.D., and colleagues at the University of Alabama at Birmingham now have identified an early biomarker of Type 1 diabetes-associated beta-cell loss in humans – microRNA-204, or miR-204.

“Serum miR-204,” Shalev said, “may provide a much needed novel approach to assess early Type 1 diabetes-associated human beta-cell loss, even before onset of overt disease.”


MicroRNAs are found in animal and plant cells, where they help control gene expression. In previous work, Shalev found that miR-204 plays key roles in regulating insulin production and other critical beta-cell processes.

Now, in a study published in the American Journal of Physiology-Endocrinology and Metabolism, Shalev and colleagues report that miR-204, which is highly enriched in human beta cells, is released by dying beta cells. After that release, it becomes detectable in circulating blood.

Measurements using human blood samples showed that serum miR-204 was elevated in children and adults with early Type 1 diabetes, and in people with autoantibodies who are at risk for Type 1 diabetes, but it was not elevated in Type 2 diabetes or another autoimmune disease. Furthermore, serum miR-204 levels were inversely correlated with remaining beta-cell function in recent-onset Type 1 diabetes.

“Having a non-invasive, straightforward method sensitive enough to detect early beta-cell loss – especially prior to the diagnosis of Type 1 diabetes – is critical in order to allow for any therapeutic intervention to be started as early as possible in the disease process and ideally before the majority of beta cells has been destroyed,” Shalev said.

Shalev is a professor in the UAB Department of Medicine’s Division of Endocrinology, Diabetes and Metabolism, and she directs the UAB Comprehensive Diabetes Center.

Discovery of the biomarker was a step-by-step, hypothesis-driven process, starting from the observation that miR-204 had 108-fold higher expression in pancreatic islet beta cells as compared to pancreatic alpha cells.

The researchers first showed that miR-204 was released by cultured rat beta cells after induction of cell death by streptozotocin. Then they showed that killing of beta cells in mice given streptozotocin led both to diabetes, as expected, and to a massive increase in serum miR-204 levels.

Next, they showed that Type 1 diabetes-associated inflammatory cytokines, which induce beta cell death, caused release of miR-204 from both cultured rat beta cells and primary human pancreatic islets.

To test miR-204 in humans, they looked at serum from people receiving autologous pancreatic islet transplantations. It is known that islet transplantation is associated with massive beta-cell death shortly after the transplantation. The researchers found that miR-204 levels in serum rose sharply, 20 to 40 minutes after islet infusion.

The researchers next found that serum miR-204 was significantly elevated in children with recent-onset Type 1 diabetes. It was also elevated nearly threefold in adults with recent onset Type 1 diabetes and more than twofold in people with autoantibodies that put them at risk for Type 1 diabetes.

In contrast, it was not significantly elevated in people with Type 2 diabetes or people with the autoimmune disease rheumatoid arthritis. It was not significantly elevated in people who have had Type 1 diabetes for a long time and have lost most of their beta cells.

Serum miR-204, Shalev and colleagues found, correlated with remaining beta-cell function, as measured by the “gold standard” of mixed-meal stimulated C-peptide area under the curve. Serum miR-204 also showed good predictive diagnostic power in the context of early Type 1 diabetes, including the ability to differentiate adult recent-onset Type 1 diabetes from Type 2 diabetes. That is useful because adults with Type 1 diabetes are often misdiagnosed when first found to have diabetes.

Shalev says the study at UAB was highly interdisciplinary. Co-authors with her on the paper, “Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss,” are Guanlan Xu, Lance A. Thielen, Junqin Chen, Truman B. Grayson, Tiffany Grimes and Fernando Ovalle, Division of Endocrinology, Diabetes and Metabolism, UAB Department of Medicine; S. Louis Bridges Jr., Division of Clinical Immunology and Rheumatology, UAB Department of Medicine; Hubert M. Tse, UAB Department of Microbiology; Blair Smith, UAB Department of Surgery; Rakesh Patel, UAB Department of Pathology; Peng Li, UAB Department of Biostatistics; and Carmella Evans-Molina, Indiana University School of Medicine, Indianapolis, Indiana.

Support came from a National Institutes of Health Human Islet Research Network award and grant and from a JDRF grant.

At UAB, Shalev holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research.

This story originally appeared on the University of Alabama at Birmingham’s UAB News website.

(Courtesy of Alabama NewsCenter)

3 years ago

O’Neal Industries gives $30 million to UAB Comprehensive Cancer Center

(UAB Cancer Center/Twitter)

O’Neal Industries Inc., a family-owned global business based in Birmingham, and its shareholders have given the largest single gift in the University of Alabama at Birmingham’s history – a $30 million donation to the Comprehensive Cancer Center. The gift will allow the center to change the lives of more patients and families through transformational cancer research, patient care, education and prevention.

The center will be known as the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham.


“The O’Neal family has built a legacy in Birmingham, first in the city’s steel industry and now in the city’s future as a biomedical and technology hub,” said Ray L. Watts, M.D., president of UAB. “UAB’s National Cancer Institute-designated Comprehensive Cancer Center is among the pre-eminent cancer centers in the world, and we are proud and grateful that our cancer center will bear the O’Neal name.”

Members of the O’Neal family have been business and political leaders in Alabama for generations. Edward O’Neal was Alabama’s 26th governor, and his son Emmet served as the state’s 34th governor. Kirkman O’Neal was a pioneer in Birmingham’s burgeoning steel industry, founding in 1921 what was to become O’Neal Steel. The family now operates O’Neal Industries Inc., the nation’s largest family-owned group of metals service centers.

“We see this gift as an opportunity to give back in a meaningful way to a cause that is important to everyone,” said Craft O’Neal, chairman and CEO of O’Neal Industries and grandson of Kirkman O’Neal. “We hope the gift will be used in ways that will yield the greatest results, accelerating progress in research, treatment and prevention of cancer and, ultimately, eliminate cancer as a major public health problem.”

The gift and naming will be formally considered for acceptance by the University of Alabama System Board of Trustees at its February meeting.

“This gift will enhance the profile and impact of the cancer center as a premier national destination for those working to end cancer, and those fighting a personal battle with the disease,” said Selwyn Vickers, M.D., senior vice president and dean of the UAB School of Medicine. “It will have lifesaving results that can serve as a catalyst for further philanthropic investment, and we are grateful to the O’Neal family and O’Neal Industries for their leadership in the fight to end cancer.”

UAB’s cancer center was one of the original eight comprehensive cancer centers established by the National Cancer Act in 1971 and has been continuously funded for 46 years.

“We have made great strides in cancer treatment and prevention in the past several decades,” said Will Ferniany, Ph.D., CEO of the UAB Health System. “In the years ahead, the promise of proton therapy, precision oncology, advanced genomics and new therapeutics should reduce the burden of cancer on individual patients and their families, and on the health care system as a whole. The generous O’Neal gift will be a driving force that transforms cancer care moving forward.”

UAB is the only National Cancer Institute-designated cancer center in its four-state region. It also maintains joint ventures with Russell Medical Center and North Alabama Medical Center and manages the Deep South Network for Cancer Control, an outreach into underserved communities in Alabama and Mississippi. The UAB Health System maintains a Cancer Community Health Network in Alabama, Florida, Georgia and Mississippi.

“This truly transformational gift will have a far-reaching impact on cancer research and patient care in our community, state and region,” said Michael J. Birrer, M.D., Ph.D., director of the center. “It strengthens our clinical operation, expands our cancer research efforts, helps translate discoveries into clinical trials, and further establishes the center as a leader in cancer research and care in the nation. The impact of this gift not only will be felt in the cancer center but will be an economic driver for Birmingham and Alabama.”

The O’Neals’ extended family has been touched by cancer. Kirkman’s son and successor, Emmet, Craft’s father, died from emergency surgery associated with colon cancer, and his daughter Libby O’Neal White was a breast cancer survivor. Her husband, David White, succumbed to cancer, as did Craft O’Neal’s mother, Mary Anne, and his brother Kirk. Additional members of the O’Neal and White families have both survived and lost their lives to cancer.

“The O’Neal and White families know too well the devastating effects of cancer, and together we were motivated by the opportunity to play a role in extending the lives of those with cancer in the region, while honoring our family members who have been afflicted by the disease,” O’Neal said.

The O’Neal Comprehensive Cancer Center at UAB is home to more than 400 scientists and physician-scientists and is involved in more than 200 clinical trials of new, promising therapeutics, many using therapies that were developed at UAB. The center treats an estimated 5,000 new patients each year.

The gift will enhance patient access and overall patient care, according to Birrer. It also will expand research efforts, potentially tripling the number of clinical trials conducted at UAB. The gift will help recruiting efforts of additional investigators and provide leverage for new grant funding.

O’Neal Industries and its shareholders have a deep history of philanthropy with UAB. Craft O’Neal is a longtime member of the cancer center’s advisory board, and over the years, O’Neal Industries and family members have supported departments across UAB, including the Comprehensive Cancer Center, the Collat School of Business, the Department of Neurology, the School of Nursing, the Comprehensive Diabetes Center and UAB Athletics.

“Our company has a nearly 100-year history here, and that will continue,” O’Neal said. “We believe in giving back to the community that has been so good to us. UAB is the economic engine of Birmingham and, to a large extent, the state of Alabama. My hope is that others will see the exciting developments at the cancer center and want to invest in its future and that of our city as well.”

Industries represents a family of six companies with a global reach. There are 80 separate business locations, including 15 international facilities on four continents, employing more than 3,200 people.

“My grandfather’s and father’s generations of O’Neal employees laid the foundation for the success we enjoy today,” O’Neal said. “This success enables us to give back in all the communities in which we are located, and do even bigger things here at our headquarters in Birmingham. I hope each of our employees, loyal customers and supportive suppliers will take pride in this gift, because without their contributions to our success, we would not be able to give back in such a meaningful way.”

(Courtesy of Alabama NewsCenter)