Angelica Parente

Building & funding the adjacent possible. Operating Partner @CivilizationVC Prev: @SHV @Nurix_Tx @Stanford @vijaypande & Bryant lab. Tweets my own🔬🧬🧠💻

[Angelica Parente @draparente]

Orchestra has been one of my favorite companies since I started working with them as a design partner 3 years ago. Anyone who has had to manage complex R&D projects understands the value of what they’ve built. So excited to see what @ashokaraj_ and @shaan_the_maan build next! @OrchestraBio @OpenAI

[Ashoka Rajendra @ashokaraj_]

Four years ago to the day, we started Orchestra Bio to help biotech and pharma teams advance their drug development programs. AI has now reached an inflection point where people and agents can take this on together. Today, we’re thrilled to share that Orchestra Bio is joining OpenAI to continue our mission at an even greater scale.

[Angelica Parente @draparente]

@WoodingtonBen @foundersfund @OpenAI Ahhh! Congrats Ben!!!!

[Angelica Parente @draparente]

Me, who deleted twitter to unplug for my birthday: “I feel so lucky to be enjoying this incredible curry donut while soaking in a footbath onsen, gazing upon this wild landscape illuminated by a misty sunny sky ”

Him, who did not: “I wonder how many millions of agents got spun up to take advantage of the cert vulnerability”

*only logged back in to downgrade my twitter subscription. See y’all again soon.

[Angelica Parente @draparente]

@ATinyGreenCell It's wild how much chronic pain can exacerbate ADHD. Attention constantly being diverted to your body's internal state. Glad you're getting help!

[Angelica Parente @draparente]

@mhdempsey @lolawajs 🤤

Best burger I've ever had in my life is at Wilder in Portland.

[Angelica Parente @draparente]

@SGRodriques @phillipzhou24 Same. It was well known at Stanford that Ed’s ideas were critical.

[Joe Sabatino @jsabatino37]

The trogocytosis plot of T cell-B cell interactions thickens!

T–B interactions yield CD3+ B cells and CD20+ T cells with pathogenic features in multiple sclerosis
https://t.co/04h0z1rz6j

[oddgoo @viriditax]

pleased to announce I’ve taken a new job at Thermo-Fisher to continue ensuring that all our assay kits are different sizes and layouts, I look forward to introducing even stranger shapes and more esoteric buffer stocks

[Angelica Parente @draparente]

@Nicole_Paulk @viriditax Who needs concentrations when you’re doing vibe science

[Angelica Parente @draparente]

@_buggles Feels like the red came very fast this year

[Angelica Parente @draparente]

@iskander The dose is the poison

[Angelica Parente @draparente]

@shelbynewsad This year I’ve started archery, photography, and recently did whitewater kayaking. Don’t think the last one will be a hobby but I would def do it again.

[Angelica Parente @draparente]

@moratowers Glad it’s been helpful!

[Angelica Parente @draparente]

@microglia_8888 Have talked to people who specialize in neurosurgical delivery and Trendelenberg position definitely helps speed up intrathecal delivery. Intracranial hypotension is also underdiagnosed and patients often get “end of day headaches” and get temporary relief from laying down.

[Foresight Institute @foresightinst]

Day two of our AI for Frontier & Meta Science workshop is kicking off in San Francisco.

Researchers, engineers, and funders are gathered for talks, working groups, and project building across neuro AI, longevity-bio, molecular nano science, and scientific infrastructure.

Yesterday's speakers included @vivnat (Google DeepMind), @tomoxl (Synchron), @dileeplearning (Astera Institute) and @alex_pentland (MIT Media Lab).

Today: @elidourado (Astera Institute), @Alexteng (Fifty Years), @draparente (Civilization Ventures), @soniaarrison (100 Plus Capital), @stuhlmueller (Elicit), and more.

Powered by @protocollabs, @paradromics, @episteme, and Future Forge Ventures.

[Angelica Parente @draparente]

Makes me wonder about B-cell depletion in the cribiform plate and how that impacts CSF antigen sampling and tolerance. Has anyone looked?

[Yan Leyfman, MD @YLeyfman]

What happens to the gut when we profoundly eliminate the B-cell compartment?

CAR-T therapy has transformed multiple myeloma, but as BCMA-directed therapies expand, we are beginning to see consequences beyond the tumor.

A new study characterizes CAR-T cell-induced enterocolitis (CAR-TEC) after cilta-cel and provides a striking look at what may be happening within the intestinal mucosa.

Using single-cell transcriptomics, flow cytometry, and tissue imaging of intestinal biopsies, investigators compared patients with CAR-TEC, CAR-T–treated patients without enterocolitis, and healthy volunteers.

They found a remarkably disrupted mucosal ecosystem:

-Profound depletion of mucosal B cells and plasma cells

-Expansion of highly cytotoxic CAR-T cells

-Inflammatory remodeling across myeloid, stromal, and glial compartments

-Telocyte-associated stromal niche dysfunction

And importantly, interferon/JAK-STAT–associated reprogramming was detected across stromal, endothelial, and epithelial compartments.

That observation provided a mechanistic rationale for targeting the pathway.

In two patients, treatment with the selective JAK1 inhibitor upadacitinib was associated with clinical, endoscopic, and histologic improvement.

The bigger story is that CAR-TEC may not simply represent “GI toxicity” from CAR-T.

It may represent a multicellular failure of mucosal homeostasis arising from profound B-cell/plasma-cell depletion, persistent immune activation, and remodeling of the intestinal tissue environment.

As B-cell–targeted therapies expand beyond oncology and into autoimmune disease, understanding what happens to the tissues that depend on these immune populations may become increasingly important.

The next frontier of CAR-T safety may be understanding not only what happens to the tumor—but what happens to the immune ecosystems surrounding it.

https://t.co/8ZBtLHGMrl

#CART #MultipleMyeloma #CellTherapy #Immunotherapy #CARTEC #Gastroenterology #TranslationalMedicine #CancerResearch

[Nick Polizzi @nickpolizzi_]

Do you use self-labeling proteins (SLPs) like HaloTag and SNAP-tag? Then check out Jody's new preprint to learn about LUCI-tag! Jody built LUCI-tag starting from K-Ras(G12C), using protein design to erase K-Ras from biology 🤯!

[Angelica Parente @draparente]

@MRauhalahti @permutans Wow new phrase added to my lexicon

[やまだ@へっぽこ研究者｜Y.KITA @tarou_ymd_]

ひとつのmRNAは、ゲノムの一箇所から作られる。この前提が崩れたかもしれない。

ハーバード大のグループが、逆転写酵素を使わない直接RNAシーケンシングでマウスのマクロファージを調べたところ、別々の遺伝子の配列がつながった「キメラmRNA」が3万種以上見つかった。その約88%は、異なる染色体どうしの組み合わせ。

炎症が起きると、離れた染色体上の遺伝子が核の中で引き寄せられ、そこでRNAが正確な一点で連結される。この接近はゲノムの折りたたみを担うCTCFに依存していた。

なかでもGsdmdとTmem106aが融合したmRNAは、データベースに存在しない新しいタンパク質をコードしていた。細胞膜であらかじめ待機し、炎症性細胞死の実行役GSDMDが穴を開けるのを加速させる「先回り役」らしい。量は本家Gsdmdの1割未満だが、1割足すだけでIL-1β放出はほぼ倍に。

マウスでは、これを失うと敗血症に強くなる一方、サルモネラ感染には弱くなった。感染防御と免疫の暴走が、同じつまみの両端にぶら下がっている。

がん細胞の異常として語られてきた融合遺伝子が、健康な細胞の正常な仕組みとしても存在する。狙える創薬標的の地図には、まだ空白がありそう。
https://t.co/6SRciFDL3h

[Angelica Parente @draparente]

@juliabelk @MartinBJensen @GordianBio I RSVP’d before realizing it’s in south SF, gonna be difficult to make it from the mission. Bummed to miss your talk @juliabelk! It was good seeing you this week @MartinBJensen.