Demystifying Medicine 2017
Tuesdays: January 10 through May 23
4:00pm - 6:00pm
Building 50 Conference Room
(unless otherwise noted)
Final Examination - Deadline is May 25, 2017 at 5:00pm ET
January 10 - Mitochondria, Aging, and Chronic Disease
Introduction by Dr. Win Arias
Why has lifespan increased in the past 50 years or more? What is the relation/mechanism linking aging with chronic diseases? What is understood about the roles of genetics, nutrition, environment, habits and physical activity?
Is there a limit as to how long people can live? What are the consequences of a population in which many/most individuals live into old age? What do centenarians die of? What are their chief complaints?
Are there animal models of aging? Does "aging" research in cells and animals inform regarding aging in humans?
At the more basic level: What has the "genomic and other -omics revolution" contributed toward understanding mechanisms of aging? How does one "study aging" in today's science?
The National institute of Aging is a major force in supporting research in aging: what are its goals, programs...and opportunities for well-trained young scientists?
In recent years, studies in cells, worms, flies and rodents have identified unexpected components of the aging process. For example, nutrient restriction, PI 3K transgenics, temperature...and others.
Associations between aging and metabolism, reactive oxygen production, mitochondrial biology and advanced cell biology have opened new avenues for exploration.
Most recently CELL 167 (7) Dec 15, 2016...Ocampo et al describe how partial reprogramming using the Yamanaka transcriptional factors ameliorated age associated hallmarks in vivo in mice! READ ALSO THE ACCOMPANYING EDITORIAL: pg 1672 entitled Bursts of reprogramming: a path to extend lifespan?
January 17 - Addiction and Habituation: Drugs and Food
What IS your understanding of the meaning of the words "addiction", "habituation" or "tolerance"?
Then consider what you think best describes the status of individuals who indulge in excessive amounts of...heroin, alcohol or food?
Neuroscientists have made huge strides in delineating mechanisms and behaviors which are shared and others which are different with regard to drugs and food. These advances, many of which have been made by today's speakers, have changed perceptions, revised ancient proposed mechanisms and continue to result in better understanding and development of treatments.
Recognition that addiction is a brain disease has permitted elucidation of neural mechanisms, identification of "therapeutic targets" and changed therapy.
From a different perspective, societal, educational, economic, beliefs and political interests add to the challenges and frustration which involves our present culture and raise major questions...the answers for which require science...and more science. For example: Should marijuana and other drugs be made to everyone? Can we modify/prevent/treat narcotic dependency?
Is excessive food consumption a habit, an addiction...or something else? Can we lose excessive weight...and sustain such loss? Is this a problem for psychologists, pharmacologists, geneticists or others?
From a societal viewpoint, these issues are critical to health. If anything, the problems are increasing. The challenges for research are abundant and critically important.
Nora Volkow, MD PhD, Director of NIDA, is a globally recognized leader in studies of addiction. Kevin Hall, PhD, Senior Investigator, NIDDK is a physicist who excitedly has bridged energy metabolism with the major clinical challenge of sustained weight reduction.
January 24 - New Approach to Atherosclerosis from Studies of Chronic Granulomatous Disease
Introduction by Dr. Win Arias
Chronic granulomatous disease (CGD) occurs in patients whose phagocytes (neutrophils and monocytes) are unable to generate antimicrobial levels of reactive oxygen species (e.g., superoxide anion) due to mutations in components of the NADPH oxidase.
Without sufficient production of superoxide anion, a key mediator of host defense, these patients suffer from life-threatening bacterial and fungal infections as well as tissue granuloma formation and other inflammatory diseases. Dr. Gallin and associates study host and microbial determinants of pathogenesis by fungal (e.g., Aspergillus fumigatus) and bacterial (e.g., Granulibacter bethesdensis) causes of infection in CGD patients. Current work focuses on the intracellular trafficking and persistence of this organism.
Genetic immunodeficiencies such as CGD also provide unique opportunities to study the roles of specific elements of the immune system in human health. For example, a clinical study employing non-invasive radiologic imaging of the cardiovascular system of CGD patients demonstrated a contribution of reactive oxygen species to the pathogenesis of atherosclerosis. Further studies are underway to evaluate the role of the NADPH oxidase in this important disease.
(see also: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929010/)
January 31 - Glycoproteins, Allergy, and Other Diseases
Introduction by Dr. Win Arias
Glycoproteins are species-specific markers and major IgE reactants in grass pollens
And produce gastrointestinal, skin and other allergic manifestations...
Glycoproteins contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein posttranslationally. modification. Secreted extracellular proteins are often glycosylated. In proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also integral membrane proteins, where they play a role in cell-cell interactions. Glycoprotein of the cytosl and nucleus can be modified through reversible addition of a single GlcNAc residues which are an additional regulatory mechanism that controls phosphorylation-based signalling. Fine processing of glycans is important for endogeneous functionality, such as cell trafficking. (see: https://en.wikipedia.org/wiki/Glycoprotein)
The inducible, nutrient-sensitive posttranslational modification of protein Ser/Thr residues with O-linked beta-N-acetylglucosamine (O-GlcNAc) occurs on histones, transcriptional regulators, metabolic enzymes, oncogenes, tumor suppressors, and many critical intermediates of growth factor signaling. O-GlcNAc cycling may serve as a homeostatic mechanism linking nutrient availability to higher-order chromatin organization. In response to nutrient availability, O-GlcNAcylation is poised to influence X chromosome inactivation and genetic imprinting, as well as embryonic development. The wide range of physiological functions regulated by O-GlcNAc cycling suggests an unexplored nexus between epigenetic regulation in disease and nutrient availability. (see: https://www.ncbi.nlm.nih.gov/pubmed/25727147)
February 7 - CANCELED: Inflammation: Cytokine Storm
February 14 - Inflammation: One Gene at a Time
Introduction by Dr. Win Arias
February 21 - Inflammation and Pancreatic Cancer
Introduction by Dr. Win Arias
February 28 - HIV: Frontiers and Vaccine Development
Although HIV has lost some public awareness and concern in many countries, the worldwide problem persists...and is prevalent in the USA, particularly in the DC and Baltimore areas. There remains huge infectivity, disease and death from HIV and its complications worldwide, particularly in southern Africa.
Diagnosis and treatment are available...but there remain problems in public health and education...as influenced by changing epidemiology and coexistence with HBV and/or HCV. Treatment has changed the disease into a treatable one...but not curable...thus treated individuals can live an almost normal life but often suffer side effects of the available targeted drugs.
Search for a vaccine has been frustrated by the complex biology of the virus...and the beneficial effect of currently available anti-HIV drugs. Nevertheless, the search goes on and progress is being made...as will be presented.
In addition, new studies of how HIV persists in treated patients and location of its hiding places continues...with exciting progress.
John Coffin, PhD (NCI/Tufts) is a frequent speaker in Demystifying Medicine and a world expert in HIV retrovirology and heads the NIH effort in this research.
Jonathan Lifson, MD (NCI) directs the vaccine research program for HIV.
March 7 - Hepatocellular Cancer and Liver Transplantation
Introduction by Dr. Win Arias - Version 1
Introduction by Dr. Win Arias - Version 2
Primary cancer of the liver mainly involves the hepatocyte...although biliary tract cells may also become neoplastic. HCC was formerly mainly a disease of the Orient and Southern Africa where HBV was demonstrated to be a causative agents. Subsequently HCV has largely replaced HBV in much of the world as an associated hepatic pathology. Although HCC usually appears in the setting of chronic active liver disease and cirrhosis, it may occur in the relative absence of these pathologies. Because of the large mass of the liver, absence of pain fibers in the liver substance (pain fibers are restricted to the liver capsule), large functional reserve and other factors, HCC is usually diagnosed late in its evolution. Furthermore, liver injury may be minimal or, as with cirrhotic liver, substantial but not specific for HCC. There are currently no well established "markers" for HCC in the circulation. Invariably, HCC is drug resistant endogenously and, therefore, chemotherapy is not successful. Advanced forms of genetically-derived therapies (antibodies, inhibitors, etc) have had negligible effect on life span or amelioration of symptoms. The only relatively successful treatment has been transplantation...for which there are strict criteria (size, shape, number of lesions). Screening of patients at risk for HCC is a huge problem given the enormous and worldwide distribution of HCV. Other factors contribute to HCC as well.
Genetic alterations in HCC are increasingly described and contribute to the malignant severity of the phenotype.
Major challenges are mechanism, molecular relation to HBV and HCV, genomic profiling of HCC, development of targeted drugs, discovery of HCC markers in plasma, etc.
These major topics will be discussed by T Jake Liang, MD NIDDK...a leading molecular hepatologist...and Lynt Johnson, MD (Georgetown University; Chairman, Department of Surgery) who is expert in liver transplantation.
March 14 - Genetic Disease Testing: Current Status and Future Prospects
The human genome has been sequenced. The era of "personalized medicine" is dawning. The role of genetics in acquired and inheritable disease is one of today's most challenging problems.
How can comprehensive genetic information be brought into the mainstream of medicine to improve the quality of health for billions of people?
Enormous advances are rapidly being made to address this question...as it pertains to complex diseases having multiple genetic components. What does it mean to be a carrier?
How is the data acquired? Analyzed? Tested? Adapted to clinical disease?
Where do we currently stand regarding this critical issue which will surely profoundly change the fae ofo medicine?
Leslie Biesecker, MD is Chief of the Medical Genomics and Metabolic Genetic Branch of NHGRI.
Robert Nussbaum, MD was formerly at NHGRI where he discovered the first genes involved in Parkinsons Disease. After being Professor of Medicine (Genetics) at UCSF, he accepted the challenge of applying comprehensive genetic information...rapidly, at low expense...for large populations...as Chief Medical Officer of Invitae.
March 21 - Fibrosis: Inflammation and Cirrhosis
In the continuing series of Demystifying Medicine sessions on "Inflammation", the March 21st session is entitled "FIBROSIS: INFLAMMATION AND CIRRHOSIS" and will be presented by Thomas Wynn PhD NIAID and Theo Heller, MD NIDDK.
Fibrosis is a critical component of wound healing; however, excess fibrosis (scarring) occurs as part of a chronic inflammatory response to varied injuries...viruses, chemicals, drugs, inborn errors, cancer and others.
Fibrosis can ultimately impair organ function of any organ. In liver, "cirrhosis" refers to chronic scarring which progressively impairs function and is life-threatening.
The major components (collagens and related proteins) are well characterized; however, their regulation remains challenging despite considerable progress. Key challenges are: Can fibrosis be reversed and function restored? Can fibrosis be prevented. Progress toward achieving these goals will be discussed.
March 28 - Obesity: Brown and Other Fat
April 4 - Sight-threatening Uveitis: a 2-way Street between Research and Clinic
Introduction to Uveitis
April 11 - Alzheimer: What, When and How
NIA Alzheimer Fact Sheet 2016
April 18 - Bioengineering: Bridging Brain, Computer, and Neurologic Disease
April 25 - Addison's Disease meets Chromatin Biology
May 2 - POSTPONED UNTIL MAY 16: Current Infectious Disease Challenges
May 9 - Schizophrenia: From Childhood to Genomes
Schizophrenia is one of the most devastating and costly mental illnesses. Early onset disease is often more severe and has stronger biological and genetic factors. Since 1990, NIMH has been recruiting patient with onset of schizophrenia before age 13. Major studies have advanced knowledge of brain development in schizophrenic patients, relation to genetic factors, predictive factors and development of therapies (Rapaport). Mice with mutants related to human psychiatric disease have been developed, characterized and used to advance knowledge of schizophrenia (Gordon).
May 16 - Current Infectious Disease Challenges
Dr. Fauci is in the forefront of knowledge and experience regarding infectious diseases which threaten the public in the United States and worldwide. Most recently, he has been deeply involved in understanding, treating and preventing global threats including HIV, Ebola, Zika, Influenza and other diseases. Emergence of new diseases having global impact is a constant threat to society and civilization itself.
Other topics will include updates as to where we stand regarding critical problems such as detection of emerging diseases, identification of :"new" infectious agents, development of vaccines and antiviral treatments...as well as global international efforts to realize that emerging infectious diseases are truly global affecting all countries and peoples.
For questions about the course, please contact email@example.com.
This web page was last modified on 11 May 2017.