A health-system-scale, episode-resolved multimodal atlas of cancer cachexia Cancer cachexia is a wasting syndrome with outsized impact on morbidity and mortality. Neither the etiology of cachexia, nor its consequences on patient physiology and outcomes, are well-understood. H...

The largest description of cancer #cachexia to date across all tumor types and over time using data from 60,000 people. @edreznik.bsky.social redefines what we know about human cachexia integrating genetics, lab values, and treatment lines. www.medrxiv.org/content/10.1...

Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer Nature Genetics - Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and...

Excited to share our latest work in collaboration with the @edreznik.bsky.social lab @mskcancercenter.bsky.social, where we describe functionally dominant mitochondrial DNA mutations in patient tumors. So, what is functional dominance in mitochondrial genetics, I hear you ask?

rdcu.be/eN1jm

For those of you hunting for your next position, please consider applying for a postdoctoral position in our lab. Our science is wild and exciting, and I promise to train and feed (yes, w/free food) you well. It doesn't hurt that we are on a publication hot streak.

Biomarker-informed care for patients with renal cell carcinoma - Nature Cancer Haake and colleagues provide an overview of recent research on biomarkers to predict immunotherapy response in clear cell renal cell carcinoma and discuss the predictive and prognostic biomarkers to p...

🚨New Review available online

Scott M. Haake and colleagues provide an overview of recent research on biomarkers to predict immunotherapy response in clear cell renal cell carcinoma and discuss the predictive and prognostic biomarkers to prioritize in this context.
www.nature.com/articles/s43...

UnitedMet harnesses RNA–metabolite covariation to impute metabolite levels in clinical samples - Nature Cancer Xie et al. present UnitedMet, a tool that leverages RNA–metabolite covariation to impute metabolite levels from transcriptomic data, and find oxidative phosphorylation associated with both BAP1 status...

🌟Technical Report online now

Amy Xie, Wesley Tansey & Ed Reznik present the tool UnitedMet that imputes metabolite levels from transcriptomic data, and find oxidative phosphorylation associated with both BAP1 status and metastasis or therapy outcome in kidney cancer.
www.nature.com/articles/s43...

Joint work with Wesley Tansey and the med-school-bound Amy Xie.

UnitedMet harnesses RNA–metabolite covariation to impute metabolite levels in clinical samples - Nature Cancer Xie et al. present UnitedMet, a tool that leverages RNA–metabolite covariation to impute metabolite levels from transcriptomic data, and find oxidative phosphorylation associated with both BAP1 status...

Excited to tell you about a new method from our lab, UnitedMet, which imputes metabolite levels/ isotope tracing from RNA data. It features the best first sentence I've ever written: "Comprehensively studying metabolism requires metabolite measurements." www.nature.com/articles/s43...

A human metabolic map of pharmacological perturbations reveals drug modes of action - Nature Biotechnology Mapping the metabolic effects of drugs helps define their mode of action.

Really cool work from @zampierilab.bsky.social
Congratulations all!!

www.nature.com/articles/s41...

Really pumped to see our paper on how mtDNA mutations modify tumour biology with @edreznik.bsky.social & colleagues highlighted by the US National Cancer Institute’s Division of Cancer Biology as one of their advances of 2024! If you’re interested do check it out 😊 www.cancer.gov/about-nci/or...

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer Selective pressure for biallelic inactivation varies widely across tumor suppressor genes and is a biomarker for therapeutic response, providing new insights into Knudson’s two-hit hypothesis.

A culmination of ~5 years of work, today our work on biallelic alterations across tumor suppressor genes is published in
@cellcellpress.bsky.social With Mark Zucker, Maria Perry, and Chai Bandlamudi www.cell.com/cell/fulltex...

This work, as with all of our work, is the product of a community. It's the collective result of the bravery of our patients, of the many conversations (with our colleagues, trainees) and collaborations (with our clinicians), and the power and joy of revisiting scientific dogma

Those re-classified VUSs have significant clinical implications. Believe it or not: biallelical loss of (VUS or driver) KEAP1 is a predictive biomarker of inferior response in LUAD. Monoallelic loss (VUS or driver!) effectively WT. Zygosity itself matters.

Selection for biallelic inactivation is also translationally useful for classifying variants of unknown significance. Look at all those VUSs in KEAP1 that are functional, as validated by a base editing screen with Francisco Sanchez-Rivera and Sam Gould

Selection for biallelic inactivation is itself a highly useful metric for identifying cryptic driver mutations. APC is a rare driver in lung and prostate cancers

Quantifying selective pressure for biallelic inactivation, we found that genes assorted in four classes based on the prevalence of selection across diseases. Class I universally selected, but many of our favorite genes (ARID1A, PIK3R1) in Class 2/3/4

We provide a foundational but missing piece of data for the field at large: a resource of how often, and in what manner, genes are biallelically inactivated. Couldn't google it before, now you can. There's lots of heterogeneity across genes, and also within genes across diseases.

The goal was to assess the selective pressure for, and functional consequences of, biallelic activation in TSGs across our prospective clinical sequencing cohort. Unexpectedly (and so therefore, expectedly), things were not as expected. Two hit hypothesis be damned!

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer Selective pressure for biallelic inactivation varies widely across tumor suppressor genes and is a biomarker for therapeutic response, providing new insights into Knudson’s two-hit hypothesis.

A culmination of ~5 years of work, today our work on biallelic alterations across tumor suppressor genes is published in
@cellcellpress.bsky.social With Mark Zucker, Maria Perry, and Chai Bandlamudi www.cell.com/cell/fulltex...