26Oct/16

“A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH” – A Synopsis

Below is a synopsis of “A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH”, a talk by Marlene Rabinovitch (MD, Stanford) given at the Vera Moulton Wall Center for Pulmonary Vascular Disease (video below). It is one of my favorite talks so far in this series of lectures… Hypothesis: there is an abnormal immune response (both innate and adaptive) affecting pulmonary arteries that is common in all forms of PAH Altered adaptive immunity in PAH pathogenesis What if antigens produced in lung are the site for autoantibody formation and immune complex deposition directly in the lung and in the perivascular area?… Read More...
22Sep/16

Lectins, Tissue Transglutaminase, & PH

As per this talk by Robb Wolf at UCSF (at ~1 hour in), non-Western Huntington’s disease carriers don’t seem to express the disease. Since Huntington’s Disease is a rare genetic neurodegenerative disease, this is intriguing and suggests that the expression of the disease may be epigenetic. As he points out a few minutes later, tissue transglutaminase has been implicated in Huntington’s Disease. What does this have to do with epigenetics and PH? Tissue transglutaminase is an enzyme that is responsible for modifying most of the body’s proteins. A key tenant of the “Paleo Diet” and similar metabolic/nutritional therapies is that consumption of dietary lectins found in grains and legumes play a role in the development of a variety of diseases by escaping into the bloodstream from the gut and triggering immune responses as well as interacting with the enzyme tissue transglutaminase.… Read More...
25Aug/16

“Interface of TH2 Inflammation and TGF-beta Signaling in Pulmonary Hypertension” – A Synopsis

Below is a synopsis of this video “Interface of TH2 Inflammation and TGF-beta Signaling in Pulmonary Hypertension”, a talk by Rubin Tuder given at the Vera Moulton Wall Center for Pulmonary Vascular Disease: Summary He has shown the first statistical correlation of perivascular inflammation with mPAP and vascular remodeling (~60 lungs from IPAH, hereditary PAH, scleroderma associated PH) despite current PH drugs: Schistosomiasis – 200 million people infected by parasite – in temperate areas like China, Brazil, Sudan, etc. 1-10% of people infected will develop PH Rather than talking about things where we don’t know what the cause/effect relationship is in PH (IPAH, Scleroderma, etc.), we should start with Schistosomiasis, which is something where we know what the culprit is: an egg nesting around vasculature that causes vasculopathy.… Read More...
13Aug/16

Pulmonary Hypertension – Atherosclerosis of the Lungs?

The passage below is from “Metabolic Regulation: A Human Perspective”, by Keith N. Frayn. I sometimes read things with a “PH filter” (and sometimes with a more global filter depending on context), and this particular passage was read with my “PH filter”… It got me thinking about the relationship of elevated non-esterified fatty acid concentrations in the plasma, adipose tissue, atherosclerosis, and if there is any connection between those and pulmonary hypertension. For some perspective, fatty acid metabolism is dysregulated in PH patients, with decreased fatty acid oxidation in myocardium and potentially increased lipid accumulation in myocardium and other tissues, increasing risk of lipotoxicity.… Read More...
12Aug/16

“Role Of T-Regulatory Cells In Immune Modulation” – A Synopsis

Below is a video and synopsis of the talk “Role Of T-Regulatory Cells In Immune Modulation” by Dr. Maria Roncarolo at the Vera Moulton Wall Center for Pulmonary Vascular Disease: Summary Standard treatment of immune mediated diseases involves anti-inflammatory and immunosuppressive drugs. By doing this, you downregulate the physiological mechanism to counteract inflammation and adaptive immune responses to self-antigens. Almost all immunosuppressive drugs block T-regulatory cell induction and function. Tolerance is not a lack of immune response, it is just a different type of immune response that the immune system puts in place when we want to tolerize an antigen (self antigen or de novo antigens) There are no drugs out there that induce tolerance to a specific antigen that we want to down-regulate Overall goal: tone down specific immune responses without completely suppressing immunity.… Read More...
08Aug/16

“Regulation Of Pulmonary Macrophage Function In Health And Disease” – A Synopsis

Below is a video and synopsis of the talk “Regulation Of Pulmonary Macrophage Function In Health And Disease” by Dr. Bruce Trapnell at the Vera Moulton Wall Center for Pulmonary Vascular Disease: Summary GM-CSF is important for macrophages to clear adenovirus transfections Normally, an adenovirus exits the endosome and is targets the nucleus of the cell and dumps its DNA into the nucleus In cells, GM-CSF redirects adenovirus to lysosomes via PU.1 GM-CSF receptor has pleiotropic effects on macrophages: low concentrations of GM-CSF leads to signaling that induces differentiation and survival of macrophages, and at higher concentrations, that pathway is shut down and another pathway occurs through the receptor that leads to growth and priming functions as well as survival.… Read More...
06Aug/16

The First CRISPR Trial In China

This month Chinese scientists are using the CRISPR method to target metastatic non-small cell lung cancer in patients. The specific technology employed will reprogram T-cells from the patients to remove the PD-1 gene. The PD-1 gene serves as a check on the cell’s ability to generate an immune response and thus prevents healthy cells from being attacked during an immune response. CRISPR is more specific than alternative immunotherapy methods (which are typically antibody based) because you are going into the cell’s genome and editing the genes. This makes CRISPR a potentially more effective method at targeting cancer cells, but it also has larger repercussions if done incorrectly.… Read More...