Missed the first run of ‘The Perils of Being Born in the Fall’ at the 2024 Hamilton Fringe Festival? Fear not, there is a repeat performance as part of the McMaster Institute for Research on Aging’s “Sage Conversations” series (and there’s free popcorn, drinks & parking – what’s not to love!)
What’s the show about? Well if you are born in September, Dr. Dawn Bowdish has got bad news for you.
Tour through the wackiness of early 19th century psychiatry, stealth mid-century reproductive rights activism and the climate/pregnancy connection; in the end you’ll learn why cold & flu season has an outsize impact on mental health.
You might laugh, but you’ll definitely learn.
Reserve a spot by clicking here
https://www.eventbrite.ca/e/sage-conversations-see-a-one-woman-show-featuring-dawn-bowdish-tickets-1016877456847
New publication alert! “Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis” Read on to learn why we did this study and why it is important. 1/n https://www.sciencedirect.com/science/article/pii/S0165247824001032?via%3Dihub
Systemic Sclerosis(SSc) is a rare autoimmune disorder that causes fibrosis of the organs. Because it is caused an immune system gone awry, patients and their doctors were concerned that their immune systems might not respond to the vaccine and leave them less protected 2/n
Because SSC is an autoimmune condition, people generally take immunosuppressive drugs, which can also lead to lower vaccine responses and higher risk of infection. We investigated whether antibody or T cell responses to vaccination were affected in SSC. 3/n
Good news! People with SSC made the same amount of antibodies to the receptor binding domain of the Spike protein (i.e, the bit of the virus that the virus uses to get into us) after their second, third, and fourth SARS-CoV-2 vaccinations. 4/n
More good news! T cell responses to vaccines are thought to help with severe disease and may offer some cross-variant protection. Following the second, third, and fourth SARS-CoV-2 vaccinations, participants with SSc had T cell responses = those without SSC. 5/n
For the immunology geeks: People living with SSc have elevated levels of serum cytokines associated with T cell differentiation. Could this change Th1/2/17/reg mix posts vaccination? Nope. 6/n
Caveat#1: This is a small study (because a rare disease) and we couldn’t investigate all the different drugs that people are on. For more info on how drugs affect vaccination responses see our other studies 7/n https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr2.11697
Caveat #2: This is very much a comparison of the quantity of immune responses, not the quality. There could still be qualitative differences in immune responses that we didn’t catch but… 8/n
…even though there is very little data on whether SSC is associated with higher infection risk or poorer outcomes what little exists doesn’t find a massive difference compared to the general population 9/n https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr.25226
Take home message #1: Participants with SSc mount similar responses to SARS-CoV-2 vaccination as controls who do not have autoimmune conditions. 10/n
Take home message #2: Many ppl with autoimmune conditions are afraid that vaccination is unsafe for them because they know their immune system is a bit wonky. It is not the disease that affects immune responses, rather it’s some, not all, drugs at some, not all, doses. 11/n
Thanks to emerging leader & 1st author Jenna Benoit (graduating & looking for a job next year – hint), rheumatologist extraordinaire, Dr. Maggie Larche, cellular immunologist Dr. J. Breznik & J Bramson, team Antibody (Nazy, Huynh) & with special thanks to…..12/n
….our participants. People with SSC often have skin changes which makes blood draws especially hard. Thank you for your commitment to our study and huge props to our exceptional phlebotomist/RC Braeden Cowbrough – our unsung hero. 13/n Fin.
This publication by former PDF, Dr Candice Quin and team, discovers that inflammatory markers and gut permeability increase with age, but the leaky gut seems to be a female specific phenomena in both mice and humans.
Bluesky explainer thread below and here https://bsky.app/profile/msmacrophage.bsky.social/post/3l5ethyexgp2u
New publication alert! “Monocyte-driven inflamm-aging reduces intestinal barrier function in females” by lead author Dr Candice Quin @uniofaberdeen.bsky.social. Read on for some surprising insights into sex differences in aging, the microbiome, inflammation, and the ‘leaky gut’ hypothesis….1/n
With age levels of inflammatory mediators (cytokines, CRP, & others) increase in the blood and tissues. This is often called ‘inflamm-aging’, and higher than age-average levels of these mediators are associated with chronic disease, frailty, and other age-associated ills. 2/n
Men & women age differently (‘men die quicker, women live sicker’)so it stands to reason they might ‘inflam-age’ differently, but very few studies on aging investigate sex differences in the aging trajectory. We looked at cellular & soluble inflammatory markers and saw sex differences! 3/n
We were surprised by the magnitude of sex differences but immunology is literally one of the worst disciplines when it comes to reporting by sex https://elifesciences.org/articles/70817
By why do we ‘inflamm-age’ in the first place? Might the mechanisms of inflamm-aging differ by sex 4/n
One of the major theories is that with age a dysbiotic microbiota causes the gut to become leaky (alternatively, the gut gets leaky with age and this alters the microbiota). Bacterial products leak out and cause inflammation. We’ve published in mice, others in other model organisms 5/n https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30112-9?elsca1=etoc&elsca2=email&elsca3=1931-3128_20170412_21_4_&elsca4=Cell%20Press
Evidence for the ‘leaky gut’ hypothesis is weak in healthy humans (despite what the probiotic industry might say). Leakiness is generally found in people who have comorbidities, or are frail so we looked at healthy/non-frail male (41) females (54) btw 20-102 yrs and were surprised to find…6/n
…that women appeared to have leakier guts over the life course (as measured by the serum marker zonulin- imperfect), and only women had evidence of an age-associated increase in the bacterial product LPS in their serum. Could the leaky gut hypothesis be female specific? 7/n
Human studies are observational so we turned to mice to understand the chain of causality. Old female, but not male, mice did indeed have leakier guts and this seemed to be caused by TNF produced by the elevated number of circulating inflammatory monocytes. 8/n
Tl;dr The age-related leaky gut -> increased circulating bacterial products -> systemic inflammation hypothesis may only be true in females! (also – always investigate sex in your research) 9/n
Why? Well the female gut changes dramatically during pregnancy to increase nutrient absorption – perhaps that is why women seem to have more permeability over the life-course. We are doing some cool ongoing studies in vitro looking at male vs female monocytes ability to break the gut barrier. 10/n
Caveats: This was a non-frail, mostly white population – aging & immunology studies show tremendous differences by location so needs to be reproduced. Gut permeability measures were done by looking at serum markers – easy on the participant but indirect at best. 11/n
Thanks to the whole (unfortunately not on Bluesky team)! This was an incredibly fun and challenging project to work on but has cemented my commitment to considering sex in all the research we do. 👩🔬🧪🦠🚨 12/12
Jessica Buckley, President and CEO of the Lung Health Foundation (LHF), and Dr. Dawn Bowdish, scientist and the Executive Director of the Firestone Institute for Respiratory Health and member of the Board of Directors of the LH talk how asthma, despite being common, can be complicated to diagnose and that many are living with uncontrolled asthma. Jessica and Dawn also share recent survey results of asthma patients’ experience, and how patients can set health goals with an asthma action plan and advocate for better air quality.
Abstract: Somatic mutations in the TET2 gene occur more frequently with age, imparting an intrinsic hematopoietic stem cells (HSCs) advantage and contributing to a phenomenon termed clonal hematopoiesis of indeterminate potential (CHIP). Individuals with TET2-mutant CHIP have a higher risk of developing myeloid neoplasms and other aging-related conditions. Despite its role in unhealthy aging, the extrinsic mechanisms driving TET2-mutant CHIP clonal expansion remain unclear. We previously showed an environment containing tumor necrosis factor (TNF) favors TET2-mutant HSC expansion in vitro. We therefore postulated that age-related increases in TNF also provide an advantage to HSCs with TET2 mutations in vivo. To test this hypothesis, we generated mixed bone marrow chimeric mice of old wild-type (WT) and TNF–/– genotypes reconstituted with WT CD45.1+ and Tet2–/– CD45.2+ HSCs. We show that age-associated increases in TNF dramatically increased the expansion
of Tet2–/– cells in old WT recipient mice, with strong skewing toward the myeloid lineage. This aberrant myelomonocytic advantage was mitigated in old TNF–/– recipient mice, suggesting that TNF signaling is essential for the expansion Tet2-mutant myeloid clones. Examination of human patients with rheumatoid arthritis with clonal hematopoiesis revealed that hematopoietic cells carrying certain mutations, including in TET2, may be sensitive to reduced TNF bioactivity following blockade with adalimumab. This suggests that targeting TNF may reduce the burden of some forms of CHIP. To our knowledge, this is the first evidence to demonstrate that TNF has a causal role in driving TET2-mutant CHIP in vivo. These findings highlight TNF as a candidate therapeutic target to control TET2-mutant CHIP.
Bluesky explainer thread here:
New Paper Alert: “Chronic TNF in the aging microenvironment exacerbates Tet2 lost-of-function myeloid expansion” published in Blood Advances #ImmunoSky #CHIP https://authors.elsevier.com/sd/article/S2473952924003860 (1/n)
Over time the progenitor cells (#stemcells) in our bone marrow acquire random mutations, with some genes being more likely to acquire these mutations than other. The Tet2 gene is one that acquires mutations. This is a problem because it regulates other genes through methylation (2/n)
Hematopoetic #stemcells with Tet2 mutations favour production of myeloid cells (#neutrophils #monocytes) over lymphoid cells (#Tcells #Bcells) and can outcompete stem cells that don’t have Tet2 mutations.(3/n)
If too many white blood cells originate from these mutants it is called Clonal Hematopoesis of Indeterminate Potential or #CHIP. CHIP is associated with an increase in mortality, and pneumonia (see prev paper), because immune cells with these mutations don’t work as well (4/n) https://shorturl.at/JNk6d
With age the proportion of Tet2 mutant cells increases and it is thought that the increased #inflammation that occurs with age contributes. Darwinian evolution happens in the bone marrow and stem cells with Tet2 mutations can outcompete (i.e. replicate more, make more white blood cells) than those without (5/n)
We investigated whether Tet2 mutant stem cells could outcompete others in the presence of the inflammatory cytokine TNF, which increases with age. We put a mix of normal and Tet2-/- stem cells into old mice that had lots of TNF and those with none (TNF KO). 6/n
Stem cells with Tet2 mutations could outcompete normal cells in old mice that had lots of TNF but not in TNF knockout mice. The aging inflammatory microenvironment contributes to CHIP! (7/n)
Cool finding- People with newly diagnosed #rheumatoidarthritis have lots of TNF and had low level of Tet2 and other CHIP mutants that went down as they started anti-TNF or anti-inflammatory therapy! Proof this happens in humans too (8/n)
Huge thank you to not on Bluesky Drs Michael Rauh (Queens), Candice Quin ( @uniofaberdeen.bsky.social ), Maggie Larche (UCalgary), Salman Basrai&Sagi Abelson @oicr.bsky.social and team. (9/9)
Born in September? Then you’re going to want to see Dr. Dawn Bowdish, scientist, and professor of medicine at McMaster University perform “The Perils of Being Born in the Fall” at this year’s Hamilton Fringe Festival (July 17-28th).
Dr. Bowdish is an award-winning scientist and first-time performer in the Hamilton Fringe Festival. Her solo show “The Perils of Being Born in the Fall” tours through the wackiness of early 19th century psychiatry, stealth mid-century reproductive rights activism, how the climate was once thought to affect your sex life, and why cold & flu season has an outsize impact on mental health.
“I’m excited to bring my love for science and science communication to a new audience. In my professional life, I need to provide facts and information in an objective and dispassionate way, but this show provides me an opportunity for me to share my passion, wonder, and amazement at the scientific process while introducing audiences to some quirky and important scientists they almost certainly wouldn’t have heard of before,” Bowdish said.
This show is a fun mix of education and entertainment, and you are guaranteed to leave with fun facts to share with your family and friends.
“The Perils of Being Born in the Fall” will be performed at as part of the Hamilton Fringe Festival at the Hamilton Theatre Inc, 140 M MacNab St N, Hamilton, ON L8R 2M3 at 7 p.m. on July 18,19,20, 25, 26, and 1.pm on July 27,and 28th.
Buy tickets here (or at the venue): https://hftco.ca/events/?mc_cid=eda1dd0bcd&mc_eid=2146b47461
For more information,follow Dr. Bowdish on Bluesky (https://bsky.app/profile/msmacrophage.bsky.social) or Instagram (https://www.instagram.com/msmacrophage/).
Let me tell you about the #BowdishLab & friend’s most recent paper “Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function”, led by Dr. C. Quin (now at @uniofaberdeen.bsky.social) @jclinical-invest.bsky.social https://www.jci.org/articles/view/171002 Tet2 is gene that is involved with methylating genes and therefore changing gene expression. Sometimes spontaneous mutations of Tet2 in hematopoetic stem cells (HSC) occur. These mutants tend to produce more myeloid cells (monocytes/neutrophils). These myeloid producing HSCs tend to be more fit in the aging bone marrow (Darwinian survival of the fittest) and overtime, more and more of your myeloid cells are made from these Tet2 mutant clones. In extreme cases this can lead to myelodysplastic disorders or cancer, but sub-clinical CHIP or clonal hematopoeisis of indeterminant potential occurs in many older adults. People with CHIP (i.e., too many of their myeloid cells are made from Tet2 mutant progenitors) are prone to all sorts of conditions (e.g., heart disease) and pneumonia. We hypothesized that pneumonia risk might be due to changes in innate immune/myeloid cell function. Mice defective in Tet2 did very poorly during Streptococcus pneumoniae infection (the most common cause of community acquired pneumonia in older adults), because their neutrophils were less able to kill bacteria. We are excited about this @jclinical-invest.bsky.social publication because it is the first mechanistic explanation for the increased risk of pneumonia in CHIP. Generally CHIP is thought to affect macrophage function, but it clearly affects neutrophil gene expression & function as well. Many thanks to Dr. Elsa Bou Ghahem for her most excellent Commentary https://www.jci.org/articles/view/181064 and for the great editorial & reviewer experience @jclinical-invest.bsky.social Research Team:Candice Quin, Erica N. DeJong, Elina K. Cook, Yi Zhen Luo, Caitlyn Vlasschaert, Sanathan Sadh, Amy J.M. McNaughton, Marco M. Buttigieg, Jessica A. Breznik, Allison E. Kennedy, Kevin Zhao, Jeffrey Mewburn, Kimberly J. Dunham-Snary, Charles C.T. Hindmarch, Alexander G. Bick, Stephen L. Archer, Michael J. Rauh, Dawn M.E. Bowdish
