Past Science Friday Talks
Prions Propagate Innate Immune Signaling
Dr. Randal Halfman, Assistant Investigator, Stowers Institute for Medical Research
Dr. Halfmann discussed recent developments in the field of prions (protein-based genetic elements), including recent work from his lab identifying essential roles for functional prions in human inflammatory signaling.
Glucocorticoids in the Prenatal Brain: Friend or Foe?
Dr. Paula Monaghan-Nichols, Associate Dean for Research, Professor Biomedical Sciences, UMKC School of Medicine
Pre-term labor is a significant health concern occurring in approximately 12% of pregnancies. Fortunately, the life threatening, emotional and economic burdens of premature birth have been greatly alleviated by antenatal treatment with synthetic glucocorticoids (sGCs).
While antenatal sGCs reduce respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis in premature infants, they can affect developmental processes in the brain and trigger adverse behavioral and metabolic outcomes later in life. Furthermore, there are significant sex and racial differences in morbidity and mortality in response to antenatal sGCs that remain unexplained, suggesting that for some infants, exposure is substandard while in others there may be overexposure.
Therefore, there is an unmet clinical need to understand the mechanistic basis for sex- and race-specific effects of sGCs on the fetal brain and develop newer antenatal sGC therapies to reduce their potential adverse neurodevelopmental effects.
We have examined the consequences of prenatal GC exposure on the developing mouse brain. Our approach includes molecular and behavioral studies, genome wide assessment of GR target genes and histological analysis of cerebral cortical development in a unique knock-in mouse model.
This talk outlined the anatomical, molecular, biochemical and behavioral alterations that result from prenatal GC exposure. We have identified a novel GC pathway that impacts proliferation of embryonic neural stem/progenitor cells and propose to use these findings to determine if they identify a genetic fingerprint for disease susceptibility in humans.
Stress-caused Mess in Aged Hearts
Dr. Xun Ai, Associate Professor, Department of Molecular Biophysics and Physiology, Rush University Medical Center
MiR-290 Cluster is an Effective Oct4 Substitute for Reprogramming Skeletal Myoblasts
Dr. Yi‐Gang Wang, Director, Regenerative Medicine Research; Professor, Department of Pathology and Laboratory Medicine, University of Cincinnati
Talk Summary - Induced pluripotent stem cells (iPSCs) have emerged as a promising resource for autologous cell-based treatments. However, widespread clinical applications are still limited by the source of somatic cells and low reprogramming efficiency. Skeletal myoblasts (SkM) have arisen as an ideal candidate somatic cell for reprogramming due to its inherited myogenic properties and the associated expression pattern of endogenous pluripotent gene programming.
Reprogramming of SkMs through introduction of the miR-290 cluster is an efficient means of promoting iPS cell production. Moreover, this miRNA cluster can replace the reprogramming master gene Oct4 to initiate somatic cell reprogramming. These results demonstrate that both miR-291a-5p and miR-291b-5p can directly target Pax7 (a myogenic marker) to enhance the iPSC generation.
Given the two roles of this miRNA cluster in somatic cell reprogramming and iPS cell pre-differentiation, the miR-290-295 derived SiPSC could be an important regulator to manipulate cardiomyocyte generation. These discoveries will facilitate elucidation of the molecular mechanisms that underlie the reprogramming process and has potential therapeutic use in the fields of biomedical research and regenerative medicine.
TDP-43: A Potential Blood-based Biomarker for Neurodegenerative Disease
Dr. Abdulbaki Agbas, Associate Professor, Division of Basic Sciences, KCU
It is estimated that about 5.1 million Americans may have Alzheimer’s disease (AD). The estimated national tab for caring for individuals with AD will reach to $1.3 trillion by 2030. Currently, there is no cure for Alzheimer’s disease. The National Plan to Address Alzheimer’s Disease calls for preventing and effectively treating AD by 2025.
The only available diagnosis is through clinical testing and FDA-approved brain scans. It is essential to develop an effective biomarker that is easy to analyze, safe and less invasive to the patients, and affordable. The earlier an accurate diagnosis of "probable" AD is made, the easier it is to manage symptoms and plan for the future.
Testing for disease modifying therapies will require proven biomarker to test for appropriate population. Current biomarkers are invasive, costly, and unproven. We have a proof of concept that a platelet-derived biomarker can distinguish AD from control and other neurodegenerative disease that can be developed for community testing.
A Journey of Discovery and Development in Cancer Therapeutics and Prevention
Dr. Jonathan White, Principal Investigator, MRIGlobal
Research in drug discovery and development is being pursued to increase throughput, decrease cost and develop medicine that demonstrates better efficacy, with greater safety margins.
Work in our lab, and at MRIGlobal, is being performed in pursuit of this goal and it covers a broad spectrum of discovery and developmental areas ranging from early discovery to preclinical investigations and onward through support of early phase clinical trials.
The TGF-beta Pathway Mediates Vascular Damage by Doxorubicin
Dr. Eugene Konorev, Associate Professor, Division of Basic Sciences, Kansas City University of Medicine and Biosciences
Recent advances in anticancer therapy improved the prognosis and survival of cancer patients. Many anticancer drugs however exhibit serious cardiovascular complications. This talk focuses on doxorubicin, an anticancer anthracycline antibiotic that is known to cause cardiomyopathy in treated patients.
Duchenne Muscular Dystrophy Gene Therapy
Dr. Dongsheng Duan, Margaret Proctor Mulligan Professor in Medical Research, Molecular Microbiology & Immunology-University of Missouri School of Medicine, Columbia, MO
Duchenne Muscular Dystrophy (DMD) is the most common lethal muscle disease. DMD is caused by dystrophin deficiency. Restoration of dystrophin expression will address the fundamental problem in DMD. In this seminar, Dr. Duan will discuss the latest development in DMD gene therapy, in particular, novel adeno-associated virus (AAV)-mediated micro- and mini-dystrophin therapy in rodent and large animal models.
Exploring Vitamin D/Vitamin D Receptor and Microbiota in Chronic Inflammation: Push the Envelope
Dr. Jun Sun, Tenured Associate Professor, University of Illinois at Chicago
Dr. Sun discussed non-classical functions of vitamin D and VDR as well as her recent findings on VDR regulation of microbiome and innate immunity in the context of health and inflammation. She addressed mechanistic concepts that underlie inflammation and cancer; and the potential therapeutic strategies to manipulate microbiota in IBD and cancer.
Contributions of Mitochondrial Polymorphisms to Cancer Metastasis
Danny Welch, PhD, Associate Director of Basic Sciences, University of Kansas Cancer Center; Founding Director of the Department of Cancer Biology and Director for National Foundation for Cancer Research Center for Metastasis Research, The University of Kansas Medical Center; Chair and professor of Cancer Biology, The University of Kansas School of Medicine; Kansas Bioscience Authority Eminent Scholar
The focus of Dr. Welch’s research is on the science of tumor progression and the regulation of cancer metastasis. His lab has developed and characterized many widely used metastasis models, discovering six of the 30 known metastasis suppressors. Dr. Welch presented published and unpublished data showing how polymorphisms in mitochondrial DNA exert pro- and anti-metastatic effects on tumor cells.
Imaging Brain Function and Metabolism In Vivo
In-Young Choi,PhD, Associate Professor of Neurology and Department of Molecular and Integrative Physiology and Director of Magnetic Resonance Science, Hoglund Brain Imaging Center at University of Kansas Medical Center
Dr. Choi's research focuses on the identification of quantitative, objective biomarkers of aging and a variety of neurological conditions such as multiple sclerosis, amyotrophic lateral sclerosis, stroke, and Alzheimer disease, primarily utilizing advanced noninvasive in vivo magnetic resonance techniques that her team has developed.
Testing Tularemia Countermeasures
Dr. Carl Gelhaus, Director of Bacterial Programs at MRIGlobal
F. Tularnesis is a highly infectious bacteria of increased interest due to its potential to use a biological/bioterror weapon. Tularemia, the disease caused by F. tularensis, can result in severe morbidity and mortality. As such, therapeutics and vaccines are needed. Dr. Carl Gelhaus has developed well characterized animal models of tularemia which closely resemble human tularemia. Dr. Gelhaus is actively testing therapeutics and vaccines and presented a recent example.
Mitochondrial Permeability Transition Pore as a Therapeutic Target of Alzheimer’s Disease
Dr. Shirley ShiDu Yan, Howard Mossberg Distinguished Professor, University of Kansas—Lawrence, KS
Mitochondria dysfunction, one of the early pathological features in Alzheimer’s disease (AD), is directly links to synaptic injury and cognitive decline. The underlying mechanisms and strategies to rescue mitochondrial and synaptic injury remain largely unknown. Her study explores the role of cyclophilin D-dependent mPTP in amyloid beta (Aβ)-induced mitochondrial and synaptic perturbation relevant to the pathogenesis of AD.