About

The Cantor Lab studies human cell physiology and how it is influenced by environmental factors with relevance to cancer and immunology.

Research topics

• Biology
• Computational biology
• Immunology
• Cell biology
• Cancer research
• Genetics

Selected publications

• Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production

  Nature Metabolism · 2026-01-16 · 1 citations

  articleSenior author
  PublisherDOI

• MassIVE MSV000100625 - HPLM_UFM - AP-MS of UFM1 in HPLM vs RPMI

  2026-01-01

  datasetOpen access1st authorCorresponding
  OA PDFDOI

• Although impaired (de)UFMylation depleted GPT2 levels regardless of growth in HPLM dS or RPMI dS, we reasoned that this pathway likely contributes to proteostasis beyond GPT2 regulation, with comprehensive impacts that might further vary based on nutrient conditions. To test this idea, we performed label-free untargeted proteomics to assess protein levels in UFM1-knockout versus control cells

  Open MIND · 2026-01-01

  other1st authorCorresponding

• MassIVE MSV000100807 - HPLM_UFM shotgun proteomics label-free

  2026-01-01

  datasetOpen access1st authorCorresponding
  OA PDFDOI

• Dynamic UFMylation governs cellular fitness by coordinating multi-organelle proteostasis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-28

  articleOpen accessSenior authorCorresponding

  ABSTRACT Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein (UBL) covalently attached to substrates through a dedicated enzymatic cascade (UFMylation) and removed by specific proteases. Despite a key role in endoplasmic reticulum (ER)-ribosome homeostasis, the basis by which this UBL supports cell fitness remains elusive, as the essentiality of UFMylation machinery varies widely across hundreds of cancer lines. Here, we trace a conditional dependence on the UFMylation pathway to the availability of alanine, an amino acid provided by human plasma-like medium but absent from most conventional synthetic media. We show that by facilitating the clearance of stalled ribosomes at the ER, dynamic UFMylation maintains cellular levels of glutamic-pyruvic transaminase 2 (GPT2), the primary enzyme responsible for de novo alanine synthesis in most human cancer lines. This buffering preserves the alanine pools required to sustain protein synthesis under alanine-restricted conditions. Beyond GPT2, UFM1 deficiency leads to widespread proteomic remodeling that spans diverse processes, including mitochondrial translation. Our results reveal that despite primarily targeting ER-localized ribosomes, the UFMylation system orchestrates a multi-organelle proteostasis network whose client composition and contributions to cell fitness are shaped by intrinsic factors and nutrient conditions.

  PublisherOA PDFDOI

• To examine whether ER localization contributes to conditional UFM1 dependence, we first assessed the composition of the active UFMylation machinery in HPLM+dS or RPMI+dS. Using UFM1-knockout cells expressing either wild-type UFM1, the conjugation-dead variant (deltaC3), or a control (RAP2A) bait, we performed Flag-based affinity purification-mass spectrometry (AP-MS).

  Open MIND · 2026-01-01

  other1st authorCorresponding

• Abstract 2489 HK2 is conditionally essential for growth in human cancer cells

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  The genetic drivers of cell growth are shaped by an interplay of intrinsic and extrinsic factors. Despite mounting evidence that gene essentiality can be modulated by cell growth conditions, there is limited consideration into how nutrient availability affects cell-essential genes. We previously tested the hypothesis that the nutrient environment affects gene essentiality in human cells. By performing CRISPR screens with blood cancer cell lines, we identified sets of genes differentially required for cells cultured in traditional (e.g., RPMI) versus Human Plasma-Like Medium (HPLM).

  PublisherOA PDFDOI

• Abstract 2261 Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis in human cells

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  NADPH is a cell-essential coenzyme that provides the major source of reducing equivalents to power macromolecule biosynthesis and antioxidant defense. The rate-limiting substrate for NADPH production is its oxidized form, NADP+, which is generated from NAD+ by NAD kinases. NADP+ and NADPH (NADP(H)) each exist in mutually exclusive pools in the mitochondria and cytosol of human cells, with compartmentalized levels of NADP(H) being controlled by two distinct NAD kinases (NADK, cytosolic; NADK2, mitochondrial).

  PublisherOA PDFDOI

• Human plasma‐like medium enhances structural and metabolic maturation of human pluripotent stem cell‐derived cardiomyocytes

  Bioengineering & Translational Medicine · 2025-11-20

  articleOpen accessCorresponding

  Abstract Maturing human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) in vitro is critical for advancing drug discovery and cardiotoxicity screening applications of these cells. However, the metabolic compositions of basal media used for hPSC‐CM culture typically offer limited relevance to human cardiac physiology. Here, we examined how culture in human plasma‐like medium (HPLM) versus conventional basal media affects the behavior of hPSC‐CMs. Starting with Day 16 hPSC‐CMs, we cultured cells for 2 weeks in either HPLM or RPMI‐based media and then assessed maturation outcomes at Day 30. Compared to RPMI/B27 media containing either RPMI‐defined (11.1 mM) or physiologic glucose levels (5 mM), HPLM/B27 enhanced hPSC‐CM maturity as evinced by concerted transcriptomic, structural, and metabolic phenotypes. These effects included a higher extent of myosin heavy chain isoform switching (α‐MHC to β‐MHC), accelerated ventricular‐specific myosin light chain isoform switching (MLC2a to MLC2v), elongated sarcomeres, increased multinucleation, enhanced calcium transient kinetics, and coordinated activation of oxidative and glycolytic metabolism. Collectively, these findings demonstrate that medium composition has substantial effects on hPSC‐CM biology and also establish HPLM as a basal medium for driving hPSC‐CM maturation in vitro.

  PublisherOA PDFDOI

• Abstract 2088 Investigating the conditional lethality of deguelin in blood cancer cells

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  Cell culture models are crucial to drug discovery because they enable high-throughput screening of chemical compounds based on phenotype or a defined molecular target.However, most anticancer therapeutics fail to translate, owing to limitations of traditional culture models.For example, most chemical screens are performed in traditional culture media such as DMEM or RPMI 1640, which poorly reflect metabolite levels that cells may face in the human body.We previously developed Human Plasma-like Medium (HPLM), a physiologic medium designed to more closely reflect the metabolic composition of human blood.By performing chemical screens in blood cancer cell lines in RPMI and HPLM, we found that nutrient conditions exert a profound influence on drug sensitivity.Among the strongest RPMI-sensitive hits from our screen results was deguelin, a derivative of rotenone that has shown efficacy in multiple cancer types.Deguelin has been suggested to act as an inhibitor of various targets involved in cell signaling pathways and metabolism, including COX2, PI3K, and mitochondrial complex I.To validate this conditional phenotype, we treated K562 chronic myeloid leukemia cells with deguelin in either RPMI or HPLM, and we observed a 30% stronger growth defect in RPMI versus HPLM.We then further recapitulated this conditional deguelin sensitivity across several blood cancer cell lines.Since the cause that may explain why cells show a stronger response to deguelin is not immediately apparent, we are currently using systematic approaches to identify the responsible drug-nutrient interaction.In addition, we are evaluating how deguelin impacts the cellular metabolome to gain unbiased insights into the mechanism of action in blood cancer cells.Overall, we expect that this work will lead to a better understanding of how deguelin inhibits cancer cell growth and could suggest approaches to improve the efficacy of deguelin by exploiting its underlying drug-nutrient interaction.

  PublisherOA PDFDOI

Frequent coauthors

• David M. Sabatini

  Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

  143 shared

• Naama Kanarek

  Massachusetts Institute of Technology

  37 shared

• Monther Abu-Remaileh

  Stanford University

  35 shared

• Elizaveta Freinkman

  Immunai (United States)

  32 shared

• Lynne Chantranupong

  Howard Hughes Medical Institute

  31 shared

• Charles H. Adelmann

  Massachusetts General Hospital

  30 shared

• Kuang Shen

  University of Massachusetts Chan Medical School

  29 shared

• Robert A. Saxton

  University of California, Berkeley

  29 shared

Labs

• Cantor LabPI