CANDLE Study

CANDLE: Conditions Affecting Neurocognitive Development and Learning in Early Childhood

Major research areas

Genetics/Biological – Blood and urine are collected from the mom at 3 time points in the study, twice before delivery and once at delivery. Cord blood and placental tissue are collected at the time of delivery also. Blood is collected from the child at age 4. With the help of Dr.’s Kyobeni Mozhui (UTHSC), Rob Williams (UTHSC), and Alicia Smith (Emory), DNA is being extracted from buffy coat, affy Axiome Biobank arrays can be run on CANDLE mother/child dyads, and CANDLE data can be linked with genetics data in Gene Network.

Neurocognitive – CANDLE children undergo cognitive assessments at ages 1, 2, and 3. These assessments look at nonverbal cognitive ability, receptive language, expressive language, motor skills, adaptive skills, and behavior observation. At age 4, the children are given a more in-depth cognitive assessment that explores overall cognitive ability, verbal skills, and nonverbal skills. Dr.’s Frederick Palmer, Carolyn Graff, Laura Murphy, Eszter Volgyi, Quynh Tran, Tamekia Jones, Toni Whitaker, Sunny Anand, and Frances Tylavsky are continually working to develop research questions focusing on neurocognitive outcomes.

Stress – CANDLE is working on putting together a team of experts who can develop research questions regarding stress and child outcomes. CANDLE  uses the Traumatic Life Events Questionnaire, Parenting Stress Index, and Social Support Questionnaire to assess stress in mothers and are collected at different time points throughout the study. Some other assessments also look at maternal depression, maternal temperament, conflict in home, and IQ.

Education – CANDLE has established a relationship with the Shelby County School District to obtain the CANDLE child’s academic and behavorial school records and hopes to follow these children throughout their school years.

Tenncare/Medical Records – CANDLE is in the process of linking its data with Medical records and Tenncare.

Public Health Exposome  – CANDLE is working with the Research Center on Health Disparities, Equity and the Exposome lead by Dr.’s Paul Juarez and Patricia Mathews-Juarez to further research economical and environmental disparities.

Other Research Areas

Demographics – Demographics data includes the SES, maternal education, race, age, marital status, and ethnicity.  CANDLE also collects data on neighborhood effects, i.e., number of individuals in household, unemployment status of neighborhood, access to fresh food in neighborhood, and perceived safety of neighborhoods. We also collected demographic information on CANDLE fathers.

Physical Health – Physical health includes the health of the child and mother. A Child Health Update is conducted on the CANDLE child every three months throughout the study. Baseline maternal health is also collected on the CANDLE mom. This includes parity, any substance abuse, and sexually transmitted diseases. Also, information regarding asthma and an extensive family history of chronic diseases and medical history is gathered. Both maternal and child blood pressure is taken at the 4 year visit.

Environmental – A Lead risk questionnaire is collected 11 times throughout the study. A choline inhibitors questionnaire is also asked 4 times during the study.

Nutrition – Two nutrition questionnaires are used for the CANDLE Study. The Food Frequency Questionnaire is collected twice for the mother to get as much information as possible about what she consumed during pregnancy. The NDSR 24-hour food recall is conducted 9 times during the course of the 3-years for the children.  There is also an Infant/Toddler Feeding Practices questionnaire and Comprehensive Feeding Practices questionnaire that look at feeding practices at different points during the child’s development.

From UTHSC News

Memphis Institute of Regenerative Medicine Recruits Global Scientific Conference to Memphis

The Memphis Institute of Regenerative Medicine (MIRM) is hosting a major international scientific conference in Memphis this fall with the Society of Experimental Biology and Medicine (SEBM) and its journal Experimental Biology and Medicine (EBM). The International Experimental Biology and Medicine Conference (IEBMC) is slated for October 8-10, 2021 at the Central Station Hotel in… Read More

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Memphis Institute of Regenerative Medicine Recruits Global Scientific Conference to Memphis

The Memphis Institute of Regenerative Medicine (MIRM) is hosting a major international scientific conference in Memphis this fall with the Society of Experimental Biology and Medicine (SEBM) and its journal Experimental Biology and Medicine (EBM).

Dr. Steve Goodman

The International Experimental Biology and Medicine Conference (IEBMC) is slated for October 8-10, 2021 at the Central Station Hotel in downtown Memphis. The annual event, which regularly attracts 250-300 attendees, is focused this year on Regenerative Medicine. Steve Goodman, PhD, vice chancellor for Research at the University of Tennessee Health Science Center, is chairing the conference planning committee, and UTHSC is supporting the event. This is the first time the global conference will take place in the United States.

Now in its eighth year, the IEBMC has become a premier international scientific meeting. Each conference highlights a different important research area, bringing thought leaders from around the globe to present as keynote and plenary speakers. This year, experts in regenerative medicine will address a wide spectrum of basic, translational and clinical research topics during five plenary sessions: Stem Cell Biology, Organs on a Chip, Organoids, Regenerative Medicine and the Cardiovascular System, and Regenerative Medicine and the Nervous System. Hiromitsu Nakauchi, MD, PhD, professor of Genetics at Stanford University is the keynote lecturer. The plenary speaker lineup includes participants from leading research Institutions across the United States and globally, the FDA Office of Tissues and Advanced Therapies, and local speakers from UTHSC and St. Jude Children’s Research Hospital.

“As a society, we are excited to host our annual international meeting in Memphis, Tennessee, on regenerative medicine, and like our past events, have organized a contemporary program with an outstanding lineup of speakers,” said Tom Thompson, PhD, University of Cincinnati College and president of SEBM.

The conference is being brought stateside for the first time, thanks to the efforts of Vice Chancellor Goodman. Dr. Goodman, who is editor-in-chief of the EBM journal, created the conference in 2013. He also spurred the creation of MIRM in 2017. MIRM performs basic, clinical, and translational research in the areas of stem cell biology, tissue engineering, production of 3D bioprinted tissues, and repair of damaged organs. Its 70 members include representatives from UTHSC, the University of Memphis (UofM), St. Jude Children’s Research Hospital, and the University of Tennessee College of Veterinary Medicine in Knoxville. Shannon Brown, Senior VP at FedEx, chairs MIRM’s Industry Advisory Committee, with Ann Burgess, former VP for Global Biologics at Wright Medical Group N.V., serving as co-chair.

SEBM, recognizing MIRM as a potential new hub for regenerative medicine in the United States, tapped Memphis as an ideal location to host an international conference on that subject. “Bringing the 2021 International Experimental Biology and Medicine Conference to Memphis is a huge win for the city, the state of Tennessee, and the University of Tennessee Health Science Center,” Dr. Goodman said. “It happened because of the converging interest of SEBM and EBM in stem cell biology and regenerative medicine and the creation of the Memphis Institute of Regenerative Medicine, which during the last three years has attracted 70 members from UTHSC, UoM, and St. Jude, and most recently, faculty from the UT College of Veterinary Medicine in Knoxville. Stem cell biology and regenerative medicine will be transformative to the practice of medicine and a major driver of economic development and job creation for Memphis, the nation and the globe in the 21st century.”

“We take great pride in co-sponsoring a conference of this magnitude right here in Memphis,” said Kennard Brown, JD, MPA, PhD, FACHE, executive vice chancellor and chief operations officer at UTHSC. “Being able to do this both highlights and underscores the clinical, research, and scientific efforts and talent in this community.”

In addition to the plenary sessions, the conference will include poster sessions and a Beale-Street themed party featuring Memphis bands is planned for conference attendees.

The conference provides an opportunity for graduate students and postdoctoral fellows to present their work to international experts on stem cell biology and regenerative medicine. Abstracts are currently being accepted, some of which will be selected for platform sessions and others for poster sessions.

For registration information or to submit an abstract, visit the event website, iebmc.org. Sponsorship opportunities are also available.  Please contact Greg Harris, senior director of Development, UT Research Foundation, at gharri28@uthsc.edu.

 

Speakers are:

 

Opening Keynote: Hiromitsu Nakauchi, MD, PhD, professor of Genetics, Stanford University

 

Session 1: Stem Cell Biology: Jian Feng, PhD, State University of New York at Buffalo ; Daniel Garry, MD, PhD, University of Minnesota; Hannele Ruohola-Baker, University of Washington; Shannon McKinney-Freeman, PhD, St. Jude Children’s Hospital

 

Session 2: Organs on a Chip: John Wikswo, PhD, Vanderbilt University; Megan McCain, PhD, University of Southern California; Hyun Jung Kim, PhD, University of Texas at Austin; Peter Loskill, PhD, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB

 

Session 3: Organoids: Antonio Santos, PhD, Stanford University; Wellington Cardoso, MD, PhD, Columbia University; Gabor Tigyi, MD, PhD, DSc, University of Tennessee Health Science Center

 

Session 4: Regenerative Medicine and the Cardiovascular System: Robert Schwartz, PhD, University of Houston; W. Keith Jones, Loyola University Chicago; Y. James Kang, PhD, University of Tennessee Health Science Center; Stuart Williams, PhD, University of Louisville

 

Session 5: Regenerative Medicine and the Nervous System: Agnes Luo, PhD, University of Cincinnati; Tatiana Segura, PhD, Duke University; Guoli Ming, MD, PhD, University of Pennsylvania; Michael Dyer, PhD, St. Jude Children’s Research Hospital

 

Closing presentation: Sung Kyung, PhD, FDA Office of Tissues and Advanced Therapies

 

Clinical Trials Network Successful in Bringing Significant Trials to UTHSC, COVID-19 Therapeutics Trial the Latest

The Clinical Trials Network of Tennessee (CTN2) at the University of Tennessee Health Science Center has contracted a new clinical trial to test possible therapeutics for COVID-19 in hospitalized patients. This new trial brings the total generated by CTN2 contracts for the university to nearly $7 million. Since its launch in 2018, CTN2 has brought… Read More

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Clinical Trials Network Successful in Bringing Significant Trials to UTHSC, COVID-19 Therapeutics Trial the Latest

The Clinical Trials Network of Tennessee (CTN2) at the University of Tennessee Health Science Center has contracted a new clinical trial to test possible therapeutics for COVID-19 in hospitalized patients. This new trial brings the total generated by CTN2 contracts for the university to nearly $7 million.

Since its launch in 2018, CTN2 has brought more than 200 clinical trial opportunities to the university and the citizens of Tennessee. Steven R. Goodman, PhD, vice chancellor for Research at UTHSC, who led the creation of CTN2, lauded “the tremendous success” of the nonprofit that enables clinical research faculty across all the UTHSC campuses, who are affiliated with hospitals, to effectively respond to opportunities for clinical trials with pharmaceutical, biotech, and medical device industry partners.

“CTN2 was created to increase the number of important clinical trials that can be conducted by our faculty, while providing credit to UTHSC for these trials and improving its national ranking as a research academic health center,” Dr. Goodman said. “The growth of CTN2 into a statewide network of 13 hospital and practice plan partners over a two-year period has been remarkable. Most importantly, these CTN2-contracted clinical trials will improve the health care of the citizens of Tennessee.”

This new trial, the third for CTN2 that involves COVID-19-related research, will evaluate the effectiveness and safety of already available drugs to treat immune system inflammation in COVID-19 patients. Immune system inflammation associated with COVID-19 has emerged as a key factor affecting the survival rate of at-risk groups.

“People with severe COVID-19 experience an inadequate immune response,” said Ivan Romero-Legro, MD, assistant professor of Pulmonary, Critical Care and Sleep Medicine at UTHSC and principal investigator of the trial. “Inflammation, the body’s reaction to an infection, is the body’s normal response to infection. If not controlled, it will lead to damaging effects on the body. We believe controlling inflammation can decrease the severity of the disease and mortality. The medications we’ll be testing have been approved for psoriatic arthritis, plaque psoriasis, rheumatoid arthritis, atopic dermatitis, and ulcerative colitis due to anti-inflammatory properties. The importance of this trial is to find a new medication to fight COVID-19 and decrease the severity of the disease in our community.”

Phil Cestaro, associate vice chancellor for Research and Business Development in the Office of Research at UTHSC, pointed out that conducting clinical trials for COVID-19 highlights the need for innovative collaborations in the health care marketplace to fight the pandemic. “Instead of individual companies running separate trials simultaneously, COVID protocols have combined various drugs under a single study. This allows for the comparison of drugs from multiple companies with the ability to include additional drugs as necessary,” Cestaro said.

Julio Lanfranco Molina, MD, associate professor of Pulmonary, Critical Care and Sleep Medicine at UTHSC, is the sub-investigator on the double-blind trial, which will be conducted at Regional One Health with patients who have been evaluated in the hospital and determined to be good candidates.

About the Clinical Trials Network of Tennessee (CTN2)

A 501(c)(3) subsidiary of the University of Tennessee Research Foundation (UTRF), CTN2 was created to increase the number of clinical trials conducted by the University of Tennessee Health Science Center’s clinical research faculty statewide. CTN2 supports UTHSC’s overarching goal of improving the health of all Tennesseans by increasing patient access to cutting-edge new therapeutics and medical devices. CTN2 provides its eight participating University of Tennessee campuses and Institutes with access to the Enterprise Data Warehouse, clinical trials budgeting and contracting, site management, site quality assurance, sponsor-relationship management, and central IRB management.

 

UTHSC’s Byron Jones Receives $2.87 Million For Gulf War Illness Study

The National Institute of Environmental Health Sciences has awarded Byron C. Jones, PhD, professor in the Department of Genetics, Geonomics, and Informatics at the University of Tennessee Health Science Center, $2.87 million for his continuing study of genetic alterations associated with Gulf War illness among former military personnel. During the 1990-91 Gulf War, 700,000 troops… Read More

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UTHSC’s Byron Jones Receives $2.87 Million For Gulf War Illness Study

Dr. Byron Jones has received a $2.87 million grant to study genetic alterations associated with Gulf War illness among former military personnel.

The National Institute of Environmental Health Sciences has awarded Byron C. Jones, PhD, professor in the Department of Genetics, Geonomics, and Informatics at the University of Tennessee Health Science Center, $2.87 million for his continuing study of genetic alterations associated with Gulf War illness among former military personnel.

During the 1990-91 Gulf War, 700,000 troops were sent to the Persian Gulf. Of those who returned, 25%-35% suffered from what became known as the Gulf War Illness, a multisymptomatic malady with complaints ranging from gastrointestinal problems to cognitive difficulties. Sickness behaviors were disabling, and neither cause nor treatment were known. Nearly 30 years later, most of those afflicted are still sick. Exposure to organophosphate compounds (nerve gas and insecticides), coupled with being in a high stress environment, have emerged as a possible cause of illness and a focus of study.

Dr. Jones’ project will build upon past studies his lab has conducted to determine why some combatants became sick, while others did not. By duplicating exposure conditions in animal models, Dr. Jones’ team has previously identified genes and biochemical pathways involved in individual differences to susceptibility.

Focusing on these systems, his team will now look for genetic-based individual differences in which genes are permanently altered in expression following the same exposure. Findings from this project will increase understanding of which biochemical processes are involved, and provide a basis for developing treatment.

“Initial studies show acute changes in proinflammatory cytokine genes and changes in methylation of genes following the exposure regimen,” Dr. Jones said. “We have seen significant differences in proinflammatory gene expression response to the treatment among animal models, and have been able to map to a region of DNA which mediates this effect. Our research takes the next steps to understand how genetics relate to the ongoing effects of Gulf War Illness.”

The study, titled “Genetics of epigenetic response to high inflammatory reducing hormones and environmental compounds,” is being funded for five years.

UTHSC Team Receives $2 Million For Diabetes Pathophysiology Study

The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded a team of UTHSC researchers $1.99 million for their work to advance understanding of the pathophysiology of prediabetes, diabetes, and related complications. Sam Dagogo-Jack, MD, professor of Medicine and director of the General Clinical Research Center, is a principal investigator, along with Nawajes… Read More

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UTHSC Team Receives $2 Million For Diabetes Pathophysiology Study

The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded a team of UTHSC researchers $1.99 million for their work to advance understanding of the pathophysiology of prediabetes, diabetes, and related complications. Sam Dagogo-Jack, MD, professor of Medicine and director of the General Clinical Research Center, is a principal investigator, along with Nawajes Mandal, PhD, associate professor in the Departments of Ophthalmology, Anatomy and Neurobiology, and Pharmaceutical Sciences. Their project is titled “Ceramides and Sphingolipids as Predictors of Incident Dysglycemia.”

Dr. Samuel Dagogo-Jack

Dr. Dagogo-Jack is a leading clinical researcher and an expert on diabetes and prediabetes. Dr. Mandal is a basic scientist and a leading expert on the role of bioactive lipid signaling, like sphingolipids (SPLs) and ceramides, in human ocular, metabolic, neurodegeneration, and inflammatory diseases. Using their combined expert perspectives, the two hypothesize that ceramides and other SPLs are critical modulators affecting the progression from normal glucose regulation, through prediabetes, to type 2 diabetes and associated diabetic complications.

To test this hypothesis, they will utilize specimens from two studies in which Dr. Dagogo-Jack is the principal investigator: the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC), which involved participants with a normal concentration of glucose who had a parental history of type 2 diabetes; and the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study (DPP/DPPOS), which followed participants already diagnosed with prediabetes for the development of type 2 diabetes. Additionally, samples from 200 individuals with normal glucose concentrations and no family history of diabetes will serve as normative controls.

The project will analyze, profile, and compare samples at baseline against various follow-up intervals to investigate several aims. Drs. Dagogo-Jack and Mandal hope to determine the role ceramide and SPLs play in prediabetes risk among people with normal glucose and a family history of type 2 diabetes, in preventive treatments for type 2 diabetes, and in the development of diabetic complications, particularly vascular disease. The project includes planned lipidomics analyses to find new predictive, prognostic and specific biomarkers for prediabetes, type 2 diabetes, and vascular complications.

Dr. Nawajes Mandal

“I am delighted that my colleague, Dr. Mandal, and I were able to pool our expertise to launch this collaborative study,” said Dr. Dagogo-Jack, who is also director of the UTHSC Division of Endocrinology, Diabetes and Metabolism. “The award from the NIH not only endorses the scientific merits of our proposal, but also gives a nod to the idea of interdisciplinary collaborative research between clinical and basic science investigators.”

“The scope of the sphingolipid system’s impact on mammalian biology has proven to be impressive, and its roles in human diseases associated with inflammation, neovascularization, tumorigenesis, and diabetes is only beginning to be understood,” said Dr. Mandal. “Our planned comprehensive analysis of ceramide regulation across the glycemic spectrum from normoglycemia through prediabetes to type 2 diabetes will unravel specific roles of ceramides and other SPLs in the pathogenesis and will provide novel SPL-related biomarkers predictive of the development and progression diabetes and its complications.”

UTHSC, UAB Collaborate on $2.39 Million Research Network

The University of Tennessee Health Science Center and the University of Alabama at Birmingham (UAB) Minority Health and Health Disparities Research Center have received a $2.39 million grant to create the Emotional Well-being and Economic Burden Research Network (EMOT-ECON). The award is from the National Center for Complementary and Integrative Health and the National Institutes of… Read More

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UTHSC, UAB Collaborate on $2.39 Million Research Network

The University of Tennessee Health Science Center and the University of Alabama at Birmingham (UAB) Minority Health and Health Disparities Research Center have received a $2.39 million grant to create the Emotional Well-being and Economic Burden Research Network (EMOT-ECON). The award is from the National Center for Complementary and Integrative Health and the National Institutes of Health Office of the Director.

Many patients suffering from the effects of COVID-19 have been left struggling with ways to pay for their treatment. However, those financial concerns also affect patients seeking cancer treatment, emergency care, surgery, and more. Furthermore, little attention has been given to how the financial consequences of a disease affect a person’s emotional well-being.

This is partly due to the lack of dedicated researchers in this field.

Dr. Maria Pisu

“We not only need more researchers, but we need researchers from different fields of study to truly understand this topic in depth,” said Maria Pisu, PhD, professor in the Division of Preventive Medicine at UAB.

Dr. Pisu, along with Michelle Martin, PhD, director of the Center for Innovation in Health Equity Research at UTHSC, and professor in UTHSC’s Department of Preventive Medicine, will collaborate to understand the relationships between financial burden, emotional well-being, and broader health outcomes.

Dr. Michelle Martin

EMOT-ECON will include researchers from different disciplines, patients and caregivers, health care providers, and others with personal or professional interest and experience with certain research topics.

Dr. Pisu and Dr. Martin’s team includes two physician scientists, David Schwartz, MD, chair of UTHSC’s Department of Radiation Oncology, and Margaret Liang, MD, assistant professor in the Department of Obstetrics and Gynecology at UAB. Health communications expert Yu-Mei Schoenberger, PhD, assistant professor in the Division of Preventive Medicine at UAB, is also part of the team.

The network’s pilot project program aims to not only increase the number of studies in EMOT-ECON research, but also attract new people to the field.

“Our work will advance understanding of financial burden and emotional well-being and generate the body of knowledge necessary for developing interventions that minimize the impact of financial burden and enhance emotional well-being,” Dr. Martin said.

Research patient advocate and president of the West Valley Ovarian Cancer Alliance, Laurel J. Pracht, applauds their efforts.

“It is past time to recognize the financial burden patients and caregivers bear to receive/afford treatment, not only of cancer, but also chronic diseases,” Pracht said. “Naturally, it impacts a patient’s quality-of-life as well as well-being.”

UTHSC’s Jonathan Wall Receives $1.79 Million To Develop New Amyloidosis Treatment

The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded Jonathan Wall, PhD, professor in the University of Tennessee Health Science Center’s Graduate School of Medicine in Knoxville, a $1.79 million grant for his study titled “Developing a Theranostic Immunotherapy for Systemic Amyloidosis.” Amyloidosis is a rare disease that occurs when abnormal protein… Read More

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UTHSC’s Jonathan Wall Receives $1.79 Million To Develop New Amyloidosis Treatment

The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded Jonathan Wall, PhD, professor in the University of Tennessee Health Science Center’s Graduate School of Medicine in Knoxville, a $1.79 million grant for his study titled “Developing a Theranostic Immunotherapy for Systemic Amyloidosis.”

Dr. Jonathan Wall

Amyloidosis is a rare disease that occurs when abnormal protein aggregates (called amyloid) build up in tissues and organs, interfering with their normal functioning. Since early stages of the disease are often asymptomatic, most patients only seek treatment once it is clinically advanced, at which time significant amyloid deposits exist in the tissues and organ damage is present. In most cases, a diagnosis of amyloidosis results from symptoms of cardiomyopathy, renal insufficiency, or peripheral neuropathy.

Current treatment focuses on limiting further production of amyloid protein in already diseased patients, but there is an urgent need to find a way to remove existing amyloid deposits.

Lab studies involving amyloid-binding antibodies or antibody fragments designed to recruit cells capable of clearing amyloid, have been successful, however, none have yet been approved for clinincal use. In this study, Dr. Wall and his team in the Amyloidosis and Cancer Theranostics Program in Knoxville aim to develop a new peptibody (a peptide-fused antibody fragment) capable of clearing amyloid deposits in tissue, that is also “readily labeled for imaging.”

Dr. Wall has devoted 26 years to studying the pathogenesis of amyloid diseases. He and his team have conducted a Phase 1 FDA-approved PET/CT imaging trial involving a synthetic peptide capable of binding to amyloid and detecting the deposits in patients. In this new proposal, he will test how effective these novel peptibodies are at recruiting macrophages (cells that can recognize, engulf and destroy amyloid) and removing amyloid, using animal models of the disease. Their aim is to identify a lead candidate to use for molecular imaging and amyloid removal in clinical trials. “Our long-term goal is to generate an immunotherapeutic peptibody that can be radiolabeled to demonstrate amyloid binding in patients,” Dr. Wall said. “The combination of identifying patients that would benefit from peptibody therapy, and an efficacious pan-amyloid reactive therapeutic could result in significant clinical benefit for patients with these devastating diseases.”

 

Dr. Jonathan Jaggar Receives $2.3 Million For Blood Pressure Research

The National Heart, Lung, and Blood Institute recently awarded Jonathan H. Jaggar, PhD, Maury Bronstein Endowed Professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), a $2.3 million grant for his study titled “PKD proteins in endothelial cells.” The proposal’s goal is to provide a new understanding of how… Read More

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Dr. Jonathan Jaggar Receives $2.3 Million For Blood Pressure Research

The National Heart, Lung, and Blood Institute recently awarded Jonathan H. Jaggar, PhD, Maury Bronstein Endowed Professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), a $2.3 million grant for his study titled “PKD proteins in endothelial cells.” The proposal’s goal is to provide a new understanding of how endothelial cells regulate blood pressure.

Dr. Jonathan Jaggar

Blood vessels provide all of our organs with oxygen and nutrients and determine blood pressure in the body. Endothelial cells, which line the inside of all blood vessels, can cause blood vessels to relax or contract, thus controlling the body’s blood pressure. Endothelial cells stop working properly during vascular diseases such as stroke and high blood pressure (hypertension), but how this happens is not fully understood. Dr. Jaggar’s project is focused on identifying the functions of two proteins in endothelial cells called PKD1 and PKD2. His lab has new evidence that PKD1 and PKD2 physically couple in endothelial cells to relax blood vessels and reduce blood pressure. His group also found that that PKD1/PKD2 signaling is altered during hypertension, which in turn inhibits their ability to relax blood vessels. In this proposal, Dr. Jaggar’s team will test the hypothesis that physiological stimuli activate PKD1/PKD2 coupling in endothelial cells. They will investigate what causes this to happen and how it produces vasodilation. They will also study the relationship between hypertension and the breakdown in PKD1/PKD2 channel signaling and the vasodilation it makes possible.

This project, which is being funded for four years, will provide significant new information about vasoregulation by endothelial cell PKD1 and PKD2 proteins. “We are excited to drive this new research direction to better understand how PKD1 and PKD2 control our body’s blood pressure and determine what happens that prevents these proteins from lowering blood pressure during hypertension,” said Dr. Jaggar.

 

Drs. Francesca-Fang Liao, Fu-Ming Zhou Receive $1.9 Million to Study Possible Dementia Causes

The National Institute of Neurological Disorders and Stroke has awarded two UTHSC researchers over $1.9 million to study the pathogenesis of white matter damage, a main contributing factor to dementia. Francesca-Fang Liao, PhD, and Fu-Ming Zhou, PhD, both professors in the Department of Pharmacology, Addiction Science, and Toxicology, are co-investigators on the project titled “Blood-brain-barrier… Read More

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Drs. Francesca-Fang Liao, Fu-Ming Zhou Receive $1.9 Million to Study Possible Dementia Causes

The National Institute of Neurological Disorders and Stroke has awarded two UTHSC researchers over $1.9 million to study the pathogenesis of white matter damage, a main contributing factor to dementia. Francesca-Fang Liao, PhD, and Fu-Ming Zhou, PhD, both professors in the Department of Pharmacology, Addiction Science, and Toxicology, are co-investigators on the project titled “Blood-brain-barrier and white matter mechanisms underlying dementia.”

Dr. Francesca-Fang Liao

Dementia is an overall term that describes a group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person’s ability to perform everyday activities. Dr. Liao has spent over five years studying specific molecular and cellular events that cause insufficient blood flow to the brain. Based on previous findings, Dr. Liao hypothesizes that degeneration of the brain’s capillary mural cells is the earliest pathological event in white matter disease, preceding blood-brain-barrier breakdown and neocortical neurodegeneration. Her findings point to a specific protein, pericyte-BMP4, as a critical initiating factor.

Dr. Liao’s team will conduct microscopic tissue imaging of small vessels controlling brain blood flow to determine when and where pericyte losses happen. The team will also profile BMP4 changes in different cell types and verify BMP4 protein upregulation in white matter pericytes using human brain cortical samples from vascular dementia cases. Finally, Dr. Liao’s lab will analyze RNA sequencing data on isolated micro vessels to identify new potential targets for treating white matter disease.

Dr. Fu-Ming Zhou

Dr. Zhou, who has spent two decades studying Parkinson’s disease, will work from the physiological angle, examining nerve conduction and impaired neurotransmitter release in animal models. His findings may provide neurophysiological evidence for what causes vascular changes in white matter, problems in the cerebral cortex, and functional loss in neurodegenerative diseases.

“Dr. Liao is a visionary scientist on vascular dementia and Alzheimer’s disease,” Dr. Zhou said. “I am delighted that we are combining our expertise and skills to investigate some difficult, but important, questions about the pathogenesis of vascular dementia and Alzheimer’s disease.”

“Vascular dementia is the second most common form of dementia after Alzheimer’s disease,” said Dr. Liao. “With Dr. Zhou joining in force, we are embarking on a new research path to underpin early molecular and cellular mechanisms distinctive for and also shared by these two major types of dementia.”

UTHSC’s Vaithianathan Receives $1.9 Million Grant for Retinal Research

Thirumalini Vaithianathan, PhD, assistant professor in the Department of Pharmacology, Addiction Science, and Toxicology at the University of Tennessee Health Science Center, has spent a decade studying molecular signaling involved in vision. She has just received $1.9 million from the National Eye Institute for her project titled, “Dynamics of calcium signals control neurotransmitter release in… Read More

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UTHSC’s Vaithianathan Receives $1.9 Million Grant for Retinal Research

Dr. Thirumalini Vaithianathan received  $1.9 million from the National Eye Institute for retinal research.

Thirumalini Vaithianathan, PhD, assistant professor in the Department of Pharmacology, Addiction Science, and Toxicology at the University of Tennessee Health Science Center, has spent a decade studying molecular signaling involved in vision. She has just received $1.9 million from the National Eye Institute for her project titled, “Dynamics of calcium signals control neurotransmitter release in retinal ribbon Synapses”.

The goal of Dr. Vaithianathan’s project is to provide a deeper understanding of calcium signaling controlling the release of chemical messengers at neural communication sites in the retina. Using animal models, she will study these submicron signals in living retinal ribbon synapses during development, normal adulthood, and disease. Dr. Vaithianathan will be using novel approaches combining state-of-the-art fluorescence imaging and voltage-clamp electrophysiology (a technique to measure ion currents across the cell membrane) to directly monitor calcium signaling in neurotransmission.

“Calcium signaling is a key player in human health and disease,” Dr. Vaithianathan said. “Our project will develop strategies to directly monitor calcium signaling in neurotransmission. We address this question particularly in the visual system for a deep and comprehensive investigation of how calcium signals control neurotransmission and encode what we ‘see’. Full understanding of calcium signaling in visual system health and disease will allow for the eventual development of therapeutic interventions to prevent and counteract neurodegeneration.”

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