About

LaShandra Sullivan is an associate professor of anthropology and co-director of the Sexualities Project at Northwestern University. She is a cultural anthropologist whose research focuses on land and property, racialized and gendered labor, and LGBTQ+ politics. Her current ethnographic and archival research is conducted in Mississippi and Brazil, where she studies practices of land holding and relations to property in her home state of Mississippi, as well as LGBTQ+ activism within the state. Additionally, she conducts ethnographic research with Black and LGBTQ+ activists in Rio de Janeiro. Sullivan has published extensively on topics related to LGBTQ activism, indigenous land struggles, and social resilience, including a book published in 2023 titled 'Unsettling Agribusiness: Indigenous Protests and Land Conflict in Brazil'.

Research topics

• Biology
• Biochemistry
• Chemistry
• Cell biology

Selected publications

• Excess cysteine reacts with sugar metabolites and impairs proliferation of NRF2-activated cancer cells

  Figshare · 2026-04-08

  datasetOpen accessSenior author

  Source Data for Crainic and Vigil et al.

  PublisherDOI

• Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2

  Cell Death and Disease · 2026-01-03

  articleOpen access

  T cell recovery is critical following damage, such as hematopoietic cell transplantation (HCT), with increased reconstitution associated with improved clinical outcomes. Endogenous thymic regeneration, a crucial process for restoring immune competence following cytoreductive therapies such as HCT conditioning, is often delayed, limiting T cell reconstitution. Fully understanding the molecular mechanisms driving regeneration is therefore crucial for uncovering therapeutic targets that can be exploited to enhance thymic function. Here, we identified that CD4+ CD8+ thymocytes rapidly and acutely undergo lytic cell death, specifically pyroptosis, following acute damage caused by ionizing radiation, and release damage-associated molecular patterns (DAMPS) into the thymic microenvironment, including ATP. Extracellular ATP stimulates the P2Y2 purinergic receptor on thymic epithelial cells (TECs)-a stromal cell crucial for supporting T cell development-resulting in the upregulation FOXN1, the master TEC transcription factor. Targeting the P2Y2 receptor with a P2Y2 agonist, UTPγS, promotes rapid regeneration of the TEC compartment in vivo following acute damage. These findings reveal a novel damage-sensing mechanism employed by the thymus where thymocytes adopt an alternative cell death mechanism which promotes thymic repair via P2Y2 signaling in TECs. This work identifies P2Y2 as a promising therapeutic target for enhancing thymus regeneration and improving immune recovery after HCT.

  PublisherOA PDFDOI

• Abstract 1788: Cysteine accumulation as a driver of resistance to bortezomib

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Covalent drugs targeting key oncogenic drivers are promising cancer therapies, but resistance limits their clinical benefit. Many covalent inhibitors rely on reacting with nucleophilic residues on proteins, and thus we hypothesized that these inhibitors could interact directly with intracellular pools of nucleophiles, like cysteine, diminishing the drug’s efficacy. To investigate the possibility that intracellular cysteine drives resistance to chemotherapies, we performed a high throughput screen of clinically available chemotherapeutics in high and low cysteine conditions. We identified cells to be more resistant to boronic-acid proteasome inhibitors in high cysteine conditions (Bortezomib (Btz) and Ixazomib (Ixa)), but not to the epoxyketone-containing proteasome inhibitor Carfilzomib (Cfz). We confirmed the potential of proteasome inhibitors to react with free cysteine and found that Btz and Ixa both formed a covalent conjugate with cysteine as detected via LC-MS. Upon treating cells with the cysteine-drug conjugate, we find nearly all of the toxicity of the drug has been abolished, supporting the hypothesis that cysteine could be a detoxification mechanism in cells. Using cancer cell lines derived from diverse cancer types, we modulated the cysteine availability and treated cells with two classes of proteasome inhibitors: those with either a boronic-acid or an epoxyketone moiety. In conditions known to increase intracellular cysteine such as high media cystine or co-treatment with the cysteine pro-drug NAC, we found that cells are more resistant to boronic acid-containing inhibitors. Conversely, when we decrease intracellular cysteine levels by co-treating with erastin, an inhibitor of SLC7A11, we measured that cells become more sensitive to Btz and Ixa. In either low or high cysteine, sensitivity to Cfz was unchanged. Collectively, these results indicate that a direct interaction between cysteine with the boronic acid group of Btz and Ixa is responsible for cysteine mediated resistance to these compounds, upstream of proteasome inhibition. We next explored cysteine’s role in rescuing proteasome function by measuring proteasome activity and ubiquitylation in cells. In both assays, we observed that high cysteine prevented the effects of proteosome in cells treated with boronic acid-containing inhibitors. We did not measure a difference in proteasome function in carfilzomib-treated cells in high cysteine, once again implying a unique direct interaction between boronic acid-containing inhibitors and cysteine. In summary, we uncovered a novel mechanism of resistance to boronic acid-containing proteasome inhibitors with straightforward possibilities to reverse resistance. This work has clinical implications for cancer treatment, especially those with ATF4 or NRF2 stabilization which both drive cysteine accumulation in a SLC7A11-dependent manner. Citation Format: Jennifer A. Brain, Sarah M. Chang, Maximilian Kobiesa, Leah G. Rector, Kelli J. Che, Zhaoqi Li, Sky H. Kim, Matthew G. Vander Heiden, Lucas B. Sullivan. Cysteine accumulation as a driver of resistance to bortezomib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1788.

  PublisherDOI

• Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells

  Nature Metabolism · 2026-04-07 · 2 citations

  articleOpen accessSenior author

  Cancer cells with constitutive NRF2 activation take up excess cystine beyond the cysteine demands of conventional pathways, implying unknown metabolic fates. Here, we develop an unbiased approach for the identification of cysteine metabolic fates and find that both known and previously uncharacterized cysteine-derived metabolites accumulate in NRF2-activated cancer cells. We identify many of these unknown metabolites as conjugates formed between cysteine and endogenous sugar metabolites, which can also be generated in vitro. We confirm the presence of these cysteine-derived conjugates in murine lung cancer models and primary human lung cancer samples, and their enrichment in NRF2-activated tumours in each context. Mechanistically, NRF2 promotes cystine uptake by driving SLC7A11 expression, which increases intracellular cysteine levels to promote these cysteine fates in a panel of cancer cell lines. Finally, we show that NRF2 activation creates a sensitivity to high environmental cystine, which impairs cell proliferation through excess free cysteine, and can be mitigated by sequestration into cysteine-derived conjugates. Overall, these findings reveal a cancer-associated metabolic vulnerability to excess cysteine stress, and reveal unrecognized routes of cysteine metabolism.

  PublisherOA PDFDOI

• Ribosome-associated quality control of aberrant protein production during amino acid limitation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-15

  articleOpen access

  Amino acids can become limiting for protein synthesis through depletion of charged tRNAs, leading to ribosome stalling and disruption of translation elongation at specific codons. To assess whether this is a mechanism by which amino acid availability can directly influence gene expression, we designed a reporter library to measure translation disruption across all sense codons in the context of amino acid limitations. We found that arginine limitation consistently impairs translation at the arginine codon AGA, resulting in synthesis of proteins from endogenous transcripts. In contrast, GCN2 pathway activation suppresses translation disruption following depletion of most other amino acids. Genome-wide screens revealed that the ribosome quality control trigger (RQC-T) and RQC pathways, which resolve ribosome collisions on defective mRNAs, catalyze ribosome splitting and premature fall-off in response to arginine depletion. Additionally, the E3 ubiquitin ligase RNF14, recently shown to clear ribosome A-site obstructions, promotes translation disruption through both ribosome fall-off and frameshifting during arginine limitation. Together, these data show that the RQC machinery is engaged by tRNA-limited ribosomes and identify a new role for RNF14 as a regulator of translation upon arginine limitation.

  PublisherDOI

• Excess cysteine reacts with sugar metabolites and impairs proliferation of NRF2-activated cancer cells

  Figshare · 2026-04-08

  datasetOpen accessSenior author

  Source Data for Crainic and Vigil et al.

  PublisherDOI

• Abstract 379: Cysteine-driven drug inactivation undermines covalent drug efficacy and drives resistance.

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Background: Constitutive activation of ATF4 drives metabolic rewiring in cancer, enhancing tumorigenesis and therapy resistance. A key consequence is upregulation of the cystine/glutamate antiporter SLC7A11, leading to increased cystine import and excessive intracellular cysteine. Cyclin-dependent kinase 7 (CDK7) inhibitors, such as YKL-5-124, are emerging anticancer agents that target proteins essential for cell proliferation. These inhibitors can be subdivided into covalent and noncovalent classes. Covalent drugs, such as YKL-5-124, act via electrophilic warheads that irreversibly react with nucleophilic amino acids, whereas noncovalent drugs, such as SY-5609, inhibit through intramolecular interactions at the protein’s active site. We hypothesized that excess intracellular nucleophiles, particularly cysteine, can sequester electrophilic drugs, reducing target engagement, and promoting resistance. Methods: We quantified the efficacy of CDK7 inhibitors in pancreatic ductal adenocarcinoma (PDAC) cell lines upon treatment conditions that alter cysteine availability. Cell growth was quantified using Sulforhodamine B (SRB) assay following drug exposure. For studies of drug-thiol reactivity, both CDK7 inhibitors were preincubated with freshly prepared cysteine (10:1 ratio, thiol:drug) in degassed PBS on ice for 1 hour, then applied to cells. For LC-MS analysis, polar metabolites were extracted from cells with 80% methanol normalized to total cell volume. Drug metabolites were measured by untargeted LC-MS using a Q-Exactive HF-X Orbitrap. Results: Pancreatic ductal adenocarcinoma (PDAC) cell lines with high SLC7A11 expression were resistant to the covalent CDK7 inhibitor YKL-5-124 compared to their low-SLC7A11 counterparts. Pharmacological inhibition of SLC7A11 with erastin sensitized high-SLC7A11 cells to YKL-5-124, whereas cotreatment of low-SLC7A11 cells with N-acetylcysteine, a cysteine prodrug, induced resistance. Sensitivity to SY-5609, a noncovalent CDK7 inhibitor, was unaffected by cysteine availability. These results suggested that cysteine may be directly acting upon covalent CDK7 inhibitors to prevent their efficacy. Indeed, pre-incubation with cysteine drastically decreased the efficacy of YKL-5-124, while SY-5609 was unaffected. LC-MS analysis detected YKL-cysteine conjugates in vitro and in cells grown under high-cystine conditions, supporting direct nucleophile-drug adduct formation. Conclusion: Elevated intracellular cysteine can chemically sequester electrophilic drugs and drive resistance. Ongoing studies aim to determine if cysteine accumulation alone suffices to confer resistance to covalent CDK7 inhibition. These results highlight cysteine metabolism as a therapeutically actionable vulnerability, potentially guiding drug selection and combination regimens for patients receiving covalent inhibitors. Citation Format: Maximilian Kobiesa, Jennifer A. Brain, Kelli J. Che, Leah G. Rector, Abby C. Jurasin, Lucas B. Sullivan. Cysteine-driven drug inactivation undermines covalent drug efficacy and drives resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 379.

  PublisherDOI

• Abstract 537: Constitutive NRF2 activation drives excess cysteine stress.

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Constitutive NRF2 activation is prevalent in human cancers and drives increased cystine uptake via SLC7A11-mediated xCT antiporter activity, exceeding cysteine demands for conventional pathways including glutathione and protein synthesis. The metabolic fates and functional consequences of this excess cysteine remain incompletely understood. To identify potentially unknown cysteine fates, we developed RMA tracing, an untargeted isotope tracing/mass spectrometry approach using equimolar mixtures of labeled [13C6,15N2] and unlabeled cystine to identify cysteine metabolic fates based on characteristic isotopologue peak pairs. Our LC-MS tracing identified 29 cysteine fates, including 20 previously unknown metabolites enriched in NRF2-activated cells and tumors. Many derived from reactions between cysteine thiols and glucose-derived sugar metabolites, forming irreversible thioether conjugates with sugar phosphates and reversible hemithioacetal/thiazolidine products with carbonyl compounds. We were able to identify these novel fates in greater abundance in NRF2-activated cultured cells, mouse tumors, and human tumor samples. We then asked if there was a functional phenotype associated with excess intracellular cysteine. We grew cells in media with increased cystine and observed a dose-dependent proliferation impairment rescued by SLC7A11 inhibition with erastin. We note this proliferation defect was independent of glutamate depletion or NADPH consumption. Additionally, inhibiting glutathione synthesis with buthionine sulfoximine intensified cysteine accumulation and proliferation defects by preventing enzymatic cysteine consumption. Alternate cysteine delivery methods (beta-mercaptoethanol or N-acetylcysteine supplementation) similarly increased intracellular cysteine and conjugate accumulation, and impaired cell growth in an SLC7A11-independent manner. We define “excess cysteine stress” as both accumulation of novel cysteine-derived metabolites and a proliferation defect in high cystine conditions. Mechanistically, we attribute NRF2 activation with this cancer-associated metabolic vulnerability to excess cysteine through constitutive SLC7A11 expression. These findings delineate novel cysteine conjugates, validate their physiological relevance across models, and identify excess cysteine stress as a distinct metabolic vulnerability in NRF2-activated cancers that may inform future therapeutic strategies. Citation Format: Jennifer A. Brain, Anna-Lena B. Vigil, Kristian Davidsen, Ayaha Itokawa, Abby C. Jurasin, Hannah J. Kerbyson, Maximilian Kobiesa, Madeleine L. Hart, Sang Jun Yoon, Gina M. DeNicola, Lucas B. Sullivan. Constitutive NRF2 activation drives excess cysteine stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 537.

  PublisherDOI

• Defined media reveal the essential role of lipid scavenging in supporting cancer cell proliferation

  Journal of Biological Chemistry · 2025-09-08 · 3 citations

  articleOpen accessSenior author

  Fetal bovine serum (FBS) is an undefined additive that is ubiquitous to mammalian cell culture media and whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS. Here, we use a combination of live-cell imaging and quantitative lipidomics to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation, with serum metal and lipid components serving as crucial metabolic resources. Despite access to a wide range of lipid classes available in serum, we find albumin-bound lipids are the primary species consumed by cancer cells. Furthermore, we find that supplementing with additives that contain necessary metals and any of the albumin-associated lipid classes can obviate the FBS requirement for cancer cell proliferation. Using this defined system, we investigated cancer cell lipid consumption dynamics, finding that albumin-associated lipids are primarily consumed through a mass-action mechanism with minimal competition within or amongst lipid classes. We also find that lipid scavenging is a dominant lipid acquisition route and is necessary for cancer cell proliferation. This work therefore identifies metabolic contributions of serum and provides a framework for building defined culture systems that sustain cell proliferation without the undefined contributions of serum.

  PublisherDOI

• In vivo functional screens reveal <i>KEAP1</i> loss as a driver of chemoresistance in small cell lung cancer

  Science Advances · 2025-04-23 · 5 citations

  articleOpen access

  Exquisitely chemosensitive initially, small cell lung cancer (SCLC) exhibits dismal outcomes owing to rapid transition to chemoresistance. Elucidating the genetic underpinnings has been challenging owing to limitations with cellular models. As SCLC patient-derived xenograft (PDX) models mimic therapeutic responses, we perform genetic screens in chemosensitive PDX models to identify drivers of chemoresistance. cDNA overexpression screens identify MYC , MYCN , and MYCL , while CRISPR deletion screens identify KEAP1 loss as driving chemoresistance. Deletion of KEAP1 switched a chemosensitive SCLC PDX model to become chemoresistant and resulted in sensitivity to inhibition of glutamine metabolism. Data from the IMpower133 clinical trial revealed ~6% of patients with extensive-stage SCLC exhibit KEAP1 genetic alterations, with activation of a KEAP1/NRF2 transcriptional signature associated with reduced survival upon chemotherapy treatment. While roles for KEAP1/NRF2 have been unappreciated in SCLC, our genetic screens revealed KEAP1 loss as a driver of chemoresistance, while patient genomic analyses demonstrate clinical importance.

  PublisherDOI

Recent grants

• Metabolic Constraints on Cancer Cell Proliferation

  NIH · $127k · 2018–2018

• Metabolic Constraints on Cancer Cell Proliferation

  NIH · $863k · 2018–2021

Frequent coauthors

• Anna-Lena B.G. Vigil

  121 shared

• Stephen R. Plymate

  University of Washington

  115 shared

• Kristian Davidsen

  Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa

  112 shared

• Hannah H. Hogan

  109 shared

• Haley J. Pang

  109 shared

• Ryan Choi

  109 shared

• Matthew M. Nguyen

  University of Washington

  109 shared

• Grant R. Whitman

  109 shared

Education

• Ph.D., Feinberg School of Medicine

  Northwestern University - Chicago

  2013

• B.S., Chemistry & Biochemistry

  California Polytechnic State University

  2007

Awards & honors

• Graduate Student Awards