E. John Wherry
@EJohnWherry
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Immunologist at University of Pennsylvania
Joined July 2013
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Delay vaccine 2nd dose? Data from Pfizer/BioNTech. After 1 dose ~100-fold lower neut Ab. 4/15 @ 30ug have none. 12/15 @ 10ug have none. Unclear if more Ab develops later. Also lowering the dose might not be great either. Note: Viruses love to evolve under partial immune pressure!
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There is no need to worry about exhaustion from a 4 vaccine dose. This is not how exhaustion works. Chronic infection with SARS-CoV-2 - that could give you exhaustion and is much (MUCH) more likely if you are unvaccinated.
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One of the most impressive T cell papers in the past decades. A truly humbling experiment and incredibly important insights into T cell biology.
@Masopust_Vezys
truly amazing. A must read for all T cell biologist (all immunologists really).
#instantclassic
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Not all vaccine side effects are bad! Injection site soreness, myalgia & fever are a sign the Immune System is working! These are "on target" effects. Unexpected, dangerous side effects should be carefully monitored. But good vaccines can, will, & should induce immune reactions
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Our paper on a detailed look an immunotypes in acute COVID-19 patients is out. Amazing team effort - so proud of all the authors involved here. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
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Our new study on immune profiling in COVID19 patients is on bioRxiv. An amazing effort by an amazing group of scientists. Not all patients respond the same way: 3 Immunotypes defined related to disease features and severity.
#ImmuneHealth
@Penn_IFI
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Excited to share our new in vivo CRISPR screening system to interrogate T cell exhaustion. Great collaboration with the amazing
@junwei_s
spearheaded by
@ZeyuCHEN19
. In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer
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Sometimes it looks like Exhausted CD8 T cells recover from exhaustion - cell surface phenotype, even RNA and scRNA..But underlying epigenetics of exhaustion can be retained, impacting future responses. Epigenetics Scarring - new work by
@M_S_Hakeem
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Today we sent a letter to FDA with >60 signatories advocating for FDA guidance in assessing T cell responses in COVID vaccine studies. T cell immunity is likely a major player in protection from disease. We should analyze T cells (with Abs and memory B cells) across studies.
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Early morning flight. KN95 for sure. Only ~30% masked here at PHL. Expect another viral blip in about 2 weeks. But don’t worry- no one will get sick. No one will get long COVID. Your employees will not call out sick for weeks…
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Last week we had a 75th bday symposium for my mentor Rafi Ahmed. His closing words should be a motto for all we do:
"This is my message to you: whatever you do, being a good human being is the most important"
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I am so incredibly humbled an honored by this award. Thank you to
@AACR
and
@CancerResearch
for all the support and to all the amazing trainees and colleagues I've been fortunate to work with.
We congratulate
@EJohnWherry
, of
@PennMedicine
on being recognized with the 2023 AACR-CRI Lloyd J. Old Award in Cancer Immunology. Learn more:
@CancerResearch
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This is incorrect. Vaccinated people can get infected with measles. This does happen. They don't get (as) sick and they don't transmit. THAT is how a
#vaccine
works.
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Really excited! Our new paper on Tox as an epigenetic and transcriptional programmer of T cell exhaustion out today in Nature (). Beautiful work by Omar Khan. Unfortunately, the wrong Fig 3 was put in this advanced online version. Correct Fig 3 attached
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Excited to share our latest review on viral persistence in
#LongCOVID
/PASC. A true team effort with a great consortium led by Amy Proal (
@microbeminded2
). See her 🧵Hoping this discussion of possible mechanisms of
#LongCovid
leads to new studies & insights
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Delighted and humbled to be elected to the AAAS Fellows together with this impressive group of friends and colleagues.
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Our new paper on rare memory CD8 T cell precursors is out! A very long road on this one... Unique DNA damage responses and PD-1 protect these rare memory CD8 T cell precursors. Amazing work by J.Johnnidis and Y.Muroyama.
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Our new paper is out on 6 month durability of mRNA vaccine immunity. Very robust memory B cell durability at 6 month with good coverage of variants and strong CD4 T cells. Great work by
@rishirajgoel
@markmpainter
and others with UPenn
#ImmuneHealth
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Our new review highlighting what we know... and also what we don't... about T cell responses in COVID-19 patients.
See new Progress article from Zeyu Chen and
@EJohnWherry
on T cell responses in patients with COVID-19
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Happy to share our latest paper by
@facts___matter
on human T cell epigenome mapping. ATAC and RNA defined human T cell subsets identify functional enhancers, fate transitions, and transcriptional and epigenetic coordination of disease relevant T cells
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A huge shout out to my team and the whole UPenn COVID Immunology effort. Amazing sample biobanking and immune profiling effort coming on line so fast. Terrific work from the Critical Care folks and so many labs at Penn pitching in. New COVID Immunology findings coming soon...
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I am excited to lead our new Colton Center for Autoimmunity at Penn. Autoimmunity affects more people than cancer. With the Colton's bold vision will allow us to investigate drivers of autoimmunity and use
#ImmuneHealth
approaches to understand & deliver new therapies to patients
Penn Medicine under John Wherry's leadership launches new Colton Center for Autoimmunity
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Exceptionally cool paper! This will be a transformative resource for the field. Congrats Nir and team!
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Another fantastic article.
@KatherineJWu
should be required reading for undergraduate biology students! We'd have a lot more immunologists in the world and that would be a great thing.
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Delighted to see our new paper in
@NatureMedicine
. Fantastic Collaboration with Amit Bar-Or and Rui Li. Great work by
@s_apostolidis
. MS patients w/o B cells still make a good T cell response to mRNA vax - in fact, CD8s are better.
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Very honored to be among the newly elected members of the American Academy of Arts and Sciences with amazing friends and colleagues
@Tcellogic
,
@FitzgeraldKate
, Ron Germain and others. Also special thanks to all the trainees in the lab over the years.
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This is why my lab won't let me near a pipet!
When the PI decides to help out in lab after being away from the bench for a few years.
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T cell responses matter during "breakthrough" SARS-CoV-2 infection. Here's new work from
@markmpainter
Really supports the notion that we should be trying to measure T cells as a correlate of protective immunity for SARS-CoV-2 (and maybe other) vaccines.
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I'm delighted to announce that I'll be taking over as Chair of the Penn Dept of Systems Pharmacology and Translational Therapeutics (on 7/1). I am honored and humbled by the opportunity. I look forward to continued excellence in the Dept and working with the amazing SPATT faculty
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My anger and frustration has now turned to every other elected republican in this country. How can the rest of you stand by and let this moron deconstruct everything we - together - have built! I try not to tweet political, but this man must be stopped!
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Reminder: Even our best vaccines e.g. measles vaccine do not prevent breakthrough infections when highly exposed. But they do prevent severe disease, long-term consequences and transmission. SARS-CoV-2 vaccines do an excellent job preventing severe disease
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Boosters in fully vaxxed healthy adults? Maybe induces modest (temporary?) immune enhancement. Scant data yet on protection. But boosting full vaxxed healthies will not end the pandemic. I hope booster discussed don't distract from getting the unvaxxed vaxxed in the US and abroad
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It's going to be a long few days of working for 30 seconds, checking the news/vote count for 5 min, rinse and repeat....
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Very excited about this new CRISPR screening work from our lab on bioRxiv. Identifying transcription factors in effector and exhausted CD8 T cells! Beautiful job by Zeyu Chen and great collaboration with Junwei Shi.
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Honored and humbled to receive the
@AACR
-CRI Lloyd J. Old Award in Cancer Immunology. Thank you
@CancerResearch
and
@AACR
. It's a privilege to try to bring our work on
#TCellExhaustion
and
#ImmuneHealth
to help improve immunotherapies for cancer and beyond.
Honored with the 2023
@AACR
-CRI Lloyd J. Old Award in Cancer Immunology at
#AACR23
, CRI Scientific Advisory Council associate director Dr. E. John Wherry
@EJohnWherry
@PennMedicine
spoke with CRI about its significance:
#Immunotherapy
#CancerResearch
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Lots to learn about mRNA SARS-CoV2 vaccines! New work from
@rishirajgoel
@s_apostolidis
@markmpainter
@divijmathew
and the UPenn Immune Health group. Are 1 or 2 doses in recovered needed? Vaccine boosting of memory B cells? Starting to see some answers.
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Scott Atlas is completely incompetent and dangerous. He should have his medical license revoked. Just because someone has a medical degree does not make them a qualified expert on any medical topic.
#stayinyourlane
White House pandemic adviser Dr. Scott Atlas appears on Russian state media and dismisses predictions about Covid-19 deaths in US
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Really excited to finally get this paper out! Role of PD-1 in memory CD8 T cell formation. Wonderful collaboration with the Sharpe lab. Stellar job from the three first authors.
The PD-1 pathway regulates development and function of memory CD8+ T cells following respiratory viral infection
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Very cool new paper using imaging mass cytometry in the brains of COVID patients. Beautiful work by
@Therealbbengsch
Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T cell interactions
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@SynthIge
Yes, thanks for responding
@aaronmring
. This is nice study showing that mRNA vaxx is, in fact, NOT associated with new autoimmune diseases... Very irresponsible tweet above by
@SynthIge
illustrating either deep scientific ineptitude or intent to deceive people about the science
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Very important study pointing out that we really need to understand the immunology of this disease ASAP.
This is a cautionary tale of how anti-Spike antibody may make COVID disease worse. In this study, the authors show that anti-Spike IgG made SARS-CoV disease worse by switching macrophage from wound-healing to proinflammatory phenotype. A thread (1/n)
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Amazing things happening at Penn! Toured our new building this week. Home for
@UPenn_I3H
,
@_ImmuneHealth_
, The Colton Center for Autoimmunity. Open mid-2025. There's an
#Immunorevolution
happening @ Penn. Exciting times Autoimmunity, Immunotherapy, CAR T, RNA science, Nobel Prize
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Here is the full text of the letter to the FDA about T cell responses in COVID vaccine studies.
Today we sent a letter to FDA with >60 signatories advocating for FDA guidance in assessing T cell responses in COVID vaccine studies. T cell immunity is likely a major player in protection from disease. We should analyze T cells (with Abs and memory B cells) across studies.
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It is not possible to overstate Tony Fauci’s impact on science and medicine. A tireless leader in infectious disease, vaccines and more for decades. His leadership will be missed. Anthony Fauci to step down as nation's top infectious disease official
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New data showing solid durability of cellular immune memory at 6 months after mRNA vaccination. Strong memory CD4 T cells and even better memory B cells. New work from
@rishirajgoel
@markmpainter
@s_apostolidis
and
@divijmathew
. UPenn
#ImmuneHealth
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Best morning I've had at work in ages! Teaching the lab how to pick LCMV plaques! Got to actually do lab work again. Why don't I go into the lab and do benchwork every day?? (I can hear my lab snickering from here....)
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Congrats to JC Beltra for his great new paper in Immunity on exhausted CD8 T cell differentiation. Subsets, developmental biology, and transcriptional and epigenetic control.
#Tcellexhaustion
.
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Even when (IF) we reach herd immunity in US important to remember this is a global problem. Variants etc a huge concern if COVID is not controlled globally. US and UK >1/3 of global vaccines so far, but =5% of the world population. Need to think and act global to end the pandemic
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Zeyu Chen's new paper in Immunity identifies early precursors of Exhausted T cells and identifies underlying molecular circuitry. Helps clarify the developmental trajectories of Tex and relationship of Tex Precursors, Progenitor and terminal Tex subsets.
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Very excited to announce a new transformative gift to UPenn
#Immunology
to fight autoimmunity. Generous support from Judy and Stewart Colton will enable major new efforts to wage a "war on autoimmunity" using
#ImmuneHealth
and great science.
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Just went back to look at this paper again. It remains one of the coolest papers of the last several years to me. Macrophages in tissues keeping non-immune cells healthy. Amazing. A Network of Macrophages Supports Mitochondrial Homeostasis in the Hea...
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Congratulations to Jim Allison
@JamesAl76228573
and Tasuku Honjo for the Nobel Prize for checkpoint blockade. A great day for immunology and immunotherapy! Lucky to be part of
@parkerici
with Jim.
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Thanks for the highlight
@SciImmunology
! Perhaps one of the more interesting papers from my lab (in my humble opinion). DNA damage / genomic surveillance properties of CD8 T cells linked to optimal memory. But only found in a small subset of the TCF1+ PD-1 hi memory precursors.
To learn about how
#Tcells
remember pathogens they've encountered,
@PennMedicine
researchers identified a self-renewing population of T cells in virus-infected mice that may be a source of full-fledged memory T cells.
Catch up on the 2021 study:
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Yes. This is a major reason why I have missed AAI many times in recent years (even pre-COVID). My wife is an amazing mother to our kids and partner in all we do. This is a choice of family over work - sorry AAI. There are plenty of other weekends in the spring for this meeting
Does not help that AAI meeting is ALWAYS on Mother’s Day
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New Viewpoints out in Nature Reviews Immunology on T cell exhaustion:
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New work from
@amylizbaxter
with
@junwei_s
and Martha Jordan. The SWI/SNF complex has received attention for its role in CD8 T cells. Now, new insights into specific control of Exhausted CD8 T cells by PBAF. Also see related work from
@Tcellogic
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Super cool new paper from
@jonepstein1
In vivo generation of CAR T cells. CAR T cells produced in vivo to treat cardiac injury
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Nice study showing vaccination reduces infectious virus upon breakthrough infection (and that viral RNA doesn't correlate well with infectious virus).
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Great article. Vaccinated people WAY less likely to spread virus. A lot of confusion about this as pointed out by
@Craig_A_Spencer
. Our messaging may have forgotten a key rules of biology - If you say "always or never" you will always be wrong.
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Super excited for our new B cell dysfunction scRNA-seq paper from Ryan Staupe now on BioRxiv (). B cells, GCs, and chronic infection!
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We were interested in immune pathways of coagulation in COVID-19. New studies from
@s_apostolidis
. Great collaborations with C.Abrams, M.Poncz & N.Meyer. Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19
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Every immunologist, virologist etc (maybe every scientist) should read this. Outstanding. Especially important when the former CDC dir. is spouting scientific nonsense to congress like the human codon for arginine is different from the bat codon. Whatt??
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Dan Barouch and I discuss the role of T cells in protection from disease for COVID-19 vaccines. Yes, Ab matter, but T cells (and memory B cells) are likely keeping folks out of the hospital. Science Magazine - T cell immunity to COVID-19 vaccines
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Very excited to be part of this outstanding new initiative to address
#LongCovid
. The efforts here should really help jumpstart our understanding of the mechanisms of
#LongCovid
and catalyze better treatments.
Today we are excited to announce the Long Covid Research Initiative - a collaboration of researchers, clinicians, and patients working to rapidly study and treat
#LongCovid
. We launch with $15M+ in funding commitments. 1/
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Celebrating
@AACR
w
@PamSharmaMDPhD
@JimAllisonPhD
@MiriamMerad
@RonDePinho
@AACRPres
Phil Greenberg
@JennGuerriero
Elaine Mardis Jim Heath Bob Schreiber
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Really cool new paper from Taku Kambayashi and colleagues. T cells induce weight loss! Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion
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New work on effector memory and exhausted CD8 T cells by
@facts___matter
's new pre-print: scRNA/ATAC defines lineages, cell identities and fates vs states. Major findings: 4 distinct TCF1+ stem-like subsets; new NK-like Tex subset and more new insights
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Check out our cool new paper from
@RaminHerati
on how Tfh in the blood can act as "biosensors" of underlying inflammatory status. A new way to use the immune system to tell use about baseline health of the host.
#ImmuneHealth
.
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An exciting new story from
@BeltraJc
identifying a role for Stat5 in counteracting Tox and major exhaustion pathways. This was also a great collaboration with Chris Garcia's lab using orthokines to turn on Stat5 in exhaustion CD8 T cells.
Our latest story is out in
@CellPressImmunity
today!! We show that Stat5 opposes Tox and rewires exhausted CD8s towards more durably protective effector-like states. Shout out to my co-authors,
@parkerici
and
@EJohnWherry
Key take-home messages in the 🧵⬇️
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Exciting new paper from
@divijmathew
highlighting the ability to drug the "immunopharmacology" of checkpoint blockade to improve responses in NSCLC. aPD1+transient JAK inhibition. A great collaboration with
@andyjminn
. Similar work from J.Teijaro
@scripps
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Michael is the godfather of viral pathogenesis and the reason so many labs have been able to use LCMV (and other viruses) for fundamental discoveries. He was an inspiration and giant in the field. I will be forever grateful to the advice he gave me early in my career. RIP MBAO
The Scripps Research community mourns the passing of Michael Oldstone, MD, esteemed virologist and professor emeritus, who helped establish the viral pathogenesis field and shaped our understanding of host immune responses
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Lot's of new work coming out on COVID in kids. Our new studies out on MedRxiv today using deep immune profiling to define distinct features of MIS-C vs non-MIS-C COVID in kids. Tour de force by
@LauraVella17
@facts___matter
@amylizbaxter
@OldridgeDerek
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Great new study from Alex Huang in the lab showing just how rapidly anti-PD-1 can reinvigorate exhausted CD8 T cells and cause robust anti-tumor effects in a subset of melanoma patients.
#Immunotherapy
@Penn_IFI
@penncancer
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Totally agree with this interpretation. 4-6 months between exposures (vaccine dose or infection) is likely a good rule of thumb. If it's been 4-6 months or more, worth getting a boost. And also agree about a great study - Congrats
@PatWilsonLab
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Congrats to Laura Mclane for her new paper on the role or nuclear localization of Tbet and Eomes in exhausted CD8 T cells (Tex)! Cytoplasmic localization of Tbet limits the activity of this TF in some Tex.
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That’s because cancer is not ONLY a genomic disease. It’s also an immunological disease and
#ImmuneHealth
and drugging the immune system in combination with genomics and drugging the cancer is needed for better outcomes
Cancer is a genomic disease and there has been extraordinary progress defining mutations that guide optimal therapy. But most patients are still not deriving the benefit of molecular markers or tumor sequencing
@NEJM
today
@rschilsky
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Amazing review on TCF1 biology in T cells from Howard Xue. A must read for anyone studying TCF1+ T cells!
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New work on T cell responses to mRNA vaccines by
@markmpainter
& team. Rapid priming of CD4 T cells that then help B cells & CD8 T cells. May explain early protection after 1 shot. Also 1 shot in recovered is enough - naive folks need 2 for full priming.
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Very exciting to see the first patient treated with this exciting and techologically advanced cellular therapy for cancer with the Integrated Circuit Techology CAR T cells from
@ArsenalBio
(). Proud to be a small part of this amazing team.
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Thrilled to be part of the new Allen Institute for Immunology. Looking forward to amazing new opportunities in human immune profiling!
Announcing the Allen Institute for Immunology, a new effort to unravel the mysteries of the immune system. Founded by the late
@PaulGAllen
, this new Institute will work to find better ways to diagnose & treat patients & to prevent immune-related diseases
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Congratulations to Liz Heller (
@EAHellerPhD
) on her promotion to Associate Professor with tenure!! It's a true pleasure and honor to work with such an amazing scientist and colleague. Congrats Liz.
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I am sure some will claim this is a 'Lab Leak' but some Flow Art for St. Patrick's day:
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Immune Health profiling of MIS-C & COVID-19 in kids. Great work by
@LauraVella17
@facts___matter
@amylizbaxter
and
@OldridgeDerek
. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19
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Super new paper from our
@LocciLab
A look into the lymph nodes in healthy and immunocompromised after vaccination. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals
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We are thrilled to welcome
@JoelBabdor
to Penn, the Department of Systems Pharmacology (
#SPATT
) the Institute for Immunology (
#IFI
) and
#ImmuneHealth
. We look forward to exciting times ahead for Immunology at Penn!
I am excited to announce that I'll be joining the University of Pennsylvania as an Asst. Professor in the Department of Systems Pharmacology and Translational Therapeutics. The
#BabdorLab
will study the dialogue between the
#Microbiome
& the
#ImmuneSystem
for
#PrecisionMedicine
.
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Someone needs to get this man a box of crayons, color-by-number book and sit him in front of a looped video of himself playing golf (and leave him there until at least November). He can't read a simple bar graph!
.
@jonathanvswan
: “Oh, you’re doing death as a proportion of cases. I’m talking about death as a proportion of population. That’s where the U.S. is really bad. Much worse than South Korea, Germany, etc.”
@realdonaldtrump
: “You can’t do that.”
Swan: “Why can’t I do that?”
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Completely agree!!
At this point, you are either vaccinated or you are going to catch Delta.
And whether you are young adult or old, when you catch Delta unvaccinated, you will have the highest chance of being hospitalized compared to almost any disease you have caught in your life.
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First rule of dogs. If they throw up, it WILL be on the rug, even if said rug only covers 2% of the floor space of the room. Just a fact.
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Scientists: Support for the innovation engine of American science: immigrants - Sign the Petition! via
@Change
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New paper from
@rishirajgoel
and
@markmpainter
. Robust memory B cells after 2 doses of mRNA vaccine. 50% of these mBc recognize Omicron and other VoC. The mBc boosted efficiently by 3rd dose. Original Wuhan-containing vaccine does a good job as a booster.
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