...the end of 2023

…we’ve come to an end of 2023, and what a year it has been!

One of my favorite things to do at the end of each year, especially in the week between Christmas and New Years is to look through the January pages of my lab notebook from that year.

I’ve been doing this subconsciously for years and while I’ve told myself the reasons were different each year. It is mostly to access the feeling of excitement, hope and “new beginnings” felt at the top of each year. One good thing about this exercise is that it relieves you from measuring yourself against traditional metrics of academic success.. such as published papers, acquired funding from grants and fellowships, citations, conference talks/presentations, invited talks, etc. Instead, it gives you a way to time-travel and access your unique creative process and measure the level of maturity of intellect that you nurture through the year from curiosity to bench.

One of the things I am most grateful for is the privilege to be an immunologist. I am not sure exactly when it all started for me, but this 18+ year journey of being an immunologist happened so organically and was never quite formalized. I remember the early days of being a technician at Sloan and just wondering what flow cytometry was all about. The ability to visualize specific markers on a cell seemed crazy and cool. Looking at cancer cells under the scope and seeing how they changed shape from a circular cell to a dendritic adhered cell on a tissue culture flask plastic.. it felt like magic. As I wrap up a couple of manuscripts for my postdoc and get ready to submit, I know it will be the end of the “training" phase of my academic career.

This week, I look back to all the late evenings of 2023, when I spend hours just staring at a piece of recent data on my second monitor. With the music in the background, view of east river outside my window.. sometimes the sanguine sunset, and sometimes the incandescent moon to join the party. Sometimes a cup of coffee and a piece of dark chocolate. But, almost ALWAYS, a version of..

“could it be?”
”shouldn’t it be?”
”Maybe it means…”
”that makes no sense! does it?”
”what was different this time?”
”I gotta repeat this!”
…and my personal favorite,

”THIS is f’ing awesome! I knew it!!!”

all of these little likely-nothings have made for some incredible and fundamental discoveries that I have (personally) made about basic lung immunology this year. As I give finishing touches to my manuscripts, I'm energized by these memories. Whether or not it will be published sooner or later will not change the level of satisfaction of figuring out some gaps. I know that it seems infantile to even articulate this, as most of us weather the highs and lows of bench science on a daily basis. But, no matter how many rejections and failures of academia we endure.. the half-life of those handful of successes in our career carry us through the decades and feed to our myopia.

So, as I wrap-up this annual reflection.. I raise my glass to all the incredible failures that are coming my way in 2024, with a promise to teach me ways to do a better, important and the most fantastic science.

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..the last harvest

It is almost the end of 2022, and I am officially done with all the bench work for the year. It has been an excruciatingly (well, seemingly) long year filled with gut-wrenching trials and trepidations in science. And as I look back to remember what I have accomplished, there have been many highs and some lows. The one thing that has been consistent throughout the year, is not taking science for granted. I have always leaned very heavily on science to find comfort and excitement, not always joy :). Looking back, I have endured a lot more physical and mental pain this year than any other. Here’s a summary of what it’s been like.

first, the highs..

memory, and protecting

Everything about memory (both immune and otherwise) is fascinating for me. The complexity with which it is procured, nurtured or coerced, enlisted and arsenalized (yep, I just made that word up) over and over ..throughout our life is truly unbelievable. I think about this concept constantly, seamlessly, tirelessly and joyously. And, I don’t just mean ..when thinking about work.. especially, off work..when I am talking to my loved ones, friends, colleagues, while watching tv, etc. So, that’s my thing. Memory. And, this year, I’ve had the privilege to think more freely about it.. than ever before. I was able to systematically gather (experimental) evidence on something I feel absolutely and intoxicatedly passionate about.. immune memory. This work has been a long time coming and will soon be available for the world to see.

Working w/ my team.

I’ve had the unbelievable honor and pleasure to work on some of the most complex aspects of science with my colleagues and mentor this year. Esp formative experience, was working on grants with my mentor. But, the process of articulating hypotheses and caveats to them, as rewarding and exciting, has instilled the realization that.. as scientists, we stand on some heavy shoulders (predecessors of discoveries) and no creative process occurs in vacuum, that thinking and writing are muscles that we develop all through our life and need to be exercised continuously.

collaborations

I part-took in a fantastic long-term highly collaborative project led by some incredible minds at NYU, Rutgers, Princeton and NIH..and it has been a formative experience for me as an immunologist. This has been exciting and grueling all the same. But, it has also made me a much better scientist and prepared me to think broadly about translational work, moving forward.

the obvious rewards

I’ve been incredibly lucky to have received a few significant research awards (ongoing F32, followed by Vilcek) that have felt like that protein bar and a glass of water..at the end of a 10mile run. There are too many reasons why this was no surprise, but many of how it just as well couldn’t have.

the γδ T cell club webinar series

I have no idea how we pulled it off, but we were able to materialize a 10-y long fantasy of finding a place to hang out with the greatest immunology minds across the globe, that specialize in the research of γδ T cells. This has been one of the most rewarding experiences of my career.

The lows..

disbelief can no longer be suspended

There are so many incredible things about science and academia. The open-ness, the permission to be wrong (rather rewarding the failures), the flexibility of being meticulous and haphazard in the same vein.. the blurring of hierarchy to work on something bigger. But, then there are the problems. The inability to adequately reward the intellectual and physical work in a monetary way. The fact that it takes so long to formalize a simple biological query into a testable hypothesis, nurture it with evidence that contextualizes the very fabric of that hypothesis and the uphill battle of getting the world to see it published. And, we’ve lost sight of the fact that.. ultimately, the bigger reason is for the world to learn from it and apply it to their own niches and continue the cycle forward.

so that’s really it for lows.. the cumbersome aspects of being a postdoc and the fact that this shall continue into the future of a faculty position, not so cheery.

Each year, this week, I kick myself for having set up an experiment that requires me to do serious bench work when I am losing steam and in dire need of a reset before the new year. I know this, because while looking through my phone .. I noticed that I have pictures of a semi-huge harvest (DM me if you do not know what this means) obvious from pictures of pathology, calculations, etc of this week, each year. It seems that I have always had experiment between Christmas and New years.. at least as far back as last 10 years, and likely even before.

And, as I wrap up the remnants of my last harvest of the year, I am filled with joy and exhaustion from the incredible year I’ve had and all the amazing things that will follow in 2023. All the incredible connections I’ve made ..both over Twitter/LinkedIN and IRL. All the wonderful conversations I’ve had about the fundamental/paradigms of immunology and so on and so forth. So, really, it isn’t “the last harvest”, but it is one more harvest, to instill the infantile joy of being an immunologist and having the privilege to challenge the paradigms and be granted failures and rise, over and over again.

/end of rant.

Covid19, antibody neutralization and the road ahead..

July 15, 2021

I recently wrote a preview for a thought-provoking study by Alexandria Tauzin et al. (Cell Host Microbe, July 2021) regarding the efficacy and associated immune responses following a single dose of BNT162b2 mRNA vaccine (by Pfizer). You can read my preview here, where I discuss some important aspects of immune response discussed in the original paper by Tauzin et al explores few interesting concepts in this study and provides moderate resolution on some burning questions.

There’s been a long-standing debate and confusion about the generation of neutralizing antibodies against SarsCov2 (N and Spike proteins), following single or double doses of mRNA vaccines. Since, I am a scientist and it’s my day job to chop up big questions into smaller pieces.. here are the main questions:

1. When will the neutralizing antibodies be generated following vaccination with 2 doses of mRNA vaccine? How much will the antibody titer be?

2. How can these be detected? What will be the quality of these antibodies?

3. Will absence or weak antibody titer correlate with weaker protection?

4. Will the amount of neutralizing antibodies differ between individuals with a history of natural infection?

5. Will the individuals with prior natural infection require two doses?

6. How will previously infected individuals respond with regards to their humoral and cellular responses?

7. Will the cellular responses fill the slack of weak neutralizing antibodies?

8. Can we predict strong correlations between Th1 and humoral responses?

It has been over 18 months, since we were made aware that a highly transmissible strain of respiratory virus had been going around, and that it has become global. By March 2020, we’d already realized that US was not safe and lock-downs were beginning to shape up. By April, we were starting to lose a disturbing number of individuals daily and it felt like we were in a war. We realized, this was deadlier than anything we had seen and we knew little about how to protect ourselves. By December 2020, however, we had vaccination available and clinical data showed protection. Science has come through and we have found unprecedented results in a historically short timeline. So, what’s next? Here’s what we still do not know:

• How long will the protection last from full vaccination regime?

• How many doses will be required to vaccinate everyone (in the world)? How much time will it take, setting aside the money issue?

Tauzin et al shows that a single dose of mRNA vaccine shows quantifiable protection (humoral and cellular) in those individuals that were previously infected. If that is true, that changes things. We would need less # of vaccine doses world-wide, especially if 12.. 18.. 24 months down the road, we need a booster. So, this is pretty significant. As an immunologist with deep interest in host-pathogen interactions, it seems like there are way too many moving parts to parse through. Focusing from the viewpoint of pathology, it is elusive (still) what contributes towards long-covid. We haven’t a concrete clue in how to prescribe and diagnose for long covid in real time, let alone… retrospectively. I want to do a follow up and connect these studies to more basic immunology as we do in the Khanna lab, to keep this stream of consciousness flowing.

Let’s keep this conversation going, so please comment/discuss your ideas.