Cartoon: Bridging the gap between advances in biology and their application to major human diseases

Demystifying Medicine 2017

Tuesdays: January 10 through May 23
4:00pm - 6:00pm
Building 50 Conference Room
(unless otherwise noted)

Main Page
Course Materials
Speaker Profiles
Topic Introductions
Final Examination

Topic Introductions

January 10 - Mitochondria, Aging, and Chronic Disease
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
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: https://irp.nih.gov/pi/john-gallin)
(see also: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929010/)


January 31 - Glycoproteins, Allergy, and Other Diseases
Glycoproteins are species-specific markers and major IgE reactants in grass pollens
Also...in foods...wine
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


March 7 - Hepatocellular Cancer and Liver Transplantation


March 14 - Genetic Disease Testing: Current Status and Future Prospects


March 21 - Fibrosis: Inflammation and Cirrhosis


March 28 - Obesity: Brown and Other Fat


April 4 - Sight-threatening Uveitis: a 2-way Street between Research and Clinic


April 11 - Alzheimer: What, When and How


April 18 - Bioengineering: Bridging Brain, Computer, and Neurologic Disease


April 25 - Addison's Disease meets Chromatin Biology


May 2 - Current Infectious Disease Challenges


May 9 - Schizophrenia: From Childhood to Genomes


May 16 - Immunotherapy of Cancer


May 23 - TITLE

 

For questions about the course, please contact ariasi@mail.nih.gov.
This web page was last modified on 21 February 2017.