About

Lorraine Gudas is a faculty member at Weill Cornell Medicine and leads the Gudas Lab, which is dedicated to understanding the actions of stem cells in cancer initiation. Her research focuses on how normal stem cells differentiate and how this process is altered during carcinogenesis. The lab also explores the functions of nutrients such as vitamin A and other retinoids in cancer prevention and in the treatment of diseases like fatty liver disease and diabetes. Dr. Gudas's work involves developing molecular pharmacological approaches to create new drugs for treating cancer, diabetes, kidney disease, and heart disease. Located on the Weill Cornell campus in New York City, Dr. Gudas's research aims to help patients with cancer or diabetes live longer and healthier lives. Her team is composed of students, postdoctoral fellows, technicians, and faculty working together to define the actions of stem cells and their role in disease. She is actively involved in mentoring and recruiting new researchers, including postdoctoral fellows, to join her team.

Research topics

• Medicine
• Biology
• Cancer research
• Internal medicine
• Cell biology
• Pathology
• Pharmacology
• Biochemistry
• Chemistry
• Urology
• Immunology
• Dentistry
• Genetics

Selected publications

• Author response for "KDM7A and KDM1A inhibition suppresses tumour promoting pathways in prostate cancer"

  2026-01-29

  peer-review
  PublisherDOI

• Abstract A023: Loss of the transcription factor ATF4 reprograms glucose metabolism in clear cell renal cell carcinoma

  Cancer Research · 2026-03-13

  articleSenior author

  Abstract Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer in adults. Transcriptomics and metabolomics studies of human ccRCC kidneys reported by others and shown in this report demonstrate upregulated glycolytic metabolism and downregulated mitochondrial oxidative processes. Abnormal and pseudohypoxic activation of hypoxia-inducible factor-1α (HIF1α) and HIF2α signaling has been considered one of the major causes of abnormal metabolisms in ccRCC. We have generated a murine TRAnsgenic model of Cancer of the Kidney (TRACK) that expresses a triple-mutant (P402A, P564A, and N803A) human HIF1α construct in murine proximal tubule cells (PTCs), interfering with the proteasomal degradation of this mutant HIF1α and enhancing its transcriptional activity in the kidneys. This mouse model mimics the early stage of ccRCC. Using this mouse model, our studies found that ATF4, a transcription factor responding to stress, is induced in ccRCC kidneys. In drosophila and cultured cells, ATF4 has been shown to be involved in regulations of glycolysis and mitochondrial oxidation. However, whether or how ATF4 regulates glycolysis and mitochondrial oxidation in ccRCC is unknown. To study the role of ATF4 in regulation of glycolysis and mitochondrial oxidation, we generated WT and TRACK ATF4-knockout (KO) mice and human RCC4 ATF4-KO cells. Using these mouse and cell lines, we demonstrate that ATF4 deletion inhibits overall glycolysis and enhances mitochondrial oxidative activities in ccRCC. Our transcriptomics and metabolomics studies in TRACK mice cooperatively show that ATF4 deletion suppresses two major steps in glycolysis and enhances several steps in the TCA cycle, particularly the step producing malate catalyzed by fumarate dehydrogenase. Our glucose tracing experiments with parental and ATF4-KO RCC4 cells demonstrate that ATF4 deletion reduced most metabolites in glycolysis and increased all metabolites in the TCA cycle, hence hindering glucose flux and enhancing the TCA cycle flux. Additional studies using Seahorse XFe96 analyzer demonstrate that inhibition of glycolysis by ATF4 deletion reduced glycolytic capacity and reserve. Enhanced mitochondrial oxidative activities by ATF4 deletion increased glucose oxidation. Together, these results demonstrate that ATF4 regulates glucose metabolism in ccRCC. ATF4 deletion can switch the carbohydrate metabolism from anaerobic to aerobic processes. Citation Format: Yuling Chi, Qiuying Chen, Eduardo Mere Del Aguila, Steven S. Gross, John A. Wagner, Shannon M. Reilly, David M. Nanus, Lorraine J. Gudas. Loss of the transcription factor ATF4 reprograms glucose metabolism in clear cell renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr A023.

  PublisherDOI

• KDM7A and KDM1A inhibition suppresses tumour promoting pathways in prostate cancer.

  Open Access CRIS of the University of Bern · 2026-03-23

  articleOpen access

  Treatment resistance has become a major challenge in cancer research, particularly for patients with advanced castration resistant prostate cancer (CRPC) where no curative therapies are available. Epigenetic alterations play a significant role in cancer progression. In prostate cancer (PCa), where androgen receptor (AR) is the primary oncogenic driver, epigenetic coregulators, specifically lysine demethylases (KDMs), have previously been identified as factors that alter the transcriptome as cancer cells acquire resistance. KDM7A has been identified as a cancer-promoting factor in many cancers; however, its role in PCa remains largely unexplored. This study investigates the clinical relevance of KDM7A in comparison with the well-studied KDM1A in PCa. Using PCa cell line models, we confirm KDM7A as an AR coregulator. By exploiting commercially available pharmacological inhibitors, we demonstrate that in AR-positive CRPC cell lines, combinatory inhibition of KDM1A and KDM7A leads to a loss of AR and the AR-driven transcriptome, which in turn attenuates cancer-promoting cell phenotypes. These findings highlight the potential of combination-targeted therapies in tackling advanced prostate cancers.

  PublisherDOI

• Alcohol dysregulation of adaptive estrogen signaling in the limbic thalamus

  Alcohol · 2026-04-07

  article
  PublisherDOI

• <scp>KDM7A</scp> and <scp>KDM1A</scp> inhibition suppresses tumour promoting pathways in prostate cancer

  Molecular Oncology · 2026-03-23

  articleOpen access

  Treatment resistance has become a major challenge in cancer research, particularly for patients with advanced castration resistant prostate cancer (CRPC) where no curative therapies are available. Epigenetic alterations play a significant role in cancer progression. In prostate cancer (PCa), where androgen receptor (AR) is the primary oncogenic driver, epigenetic coregulators, specifically lysine demethylases (KDMs), have previously been identified as factors that alter the transcriptome as cancer cells acquire resistance. KDM7A has been identified as a cancer-promoting factor in many cancers; however, its role in PCa remains largely unexplored. This study investigates the clinical relevance of KDM7A in comparison with the well-studied KDM1A in PCa. Using PCa cell line models, we confirm KDM7A as an AR coregulator. By exploiting commercially available pharmacological inhibitors, we demonstrate that in AR-positive CRPC cell lines, combinatory inhibition of KDM1A and KDM7A leads to a loss of AR and the AR-driven transcriptome, which in turn attenuates cancer-promoting cell phenotypes. These findings highlight the potential of combination-targeted therapies in tackling advanced prostate cancers.

  PublisherDOI

• ATF4 in proximal tubules modulates kidney function and modifies the metabolome

  Journal of Molecular Medicine · 2025-06-21

  articleOpen accessSenior author

  Activating transcription factor 4 (ATF4) is a transcription factor that mediates the response to stress at the cellular, tissue, and organism level. We deleted the gene encoding ATF4 in the proximal tubules of the mouse kidney by using a temporal and cell type-specific approach. We show that ATF4 plays a major role in regulating the transcriptome and proteome, which, in turn, influences the metabolome and kidney functions. Genome-wide transcriptomics and single-plot, solid-phase-enhanced sample preparation (SP3)-proteomics studies reveal that ATF4 deletion changes more than 30% of transcripts and, similarly, corresponding proteins in the proximal tubules. Gene Set Enrichment Analysis indicates major changes in transporters, including amino acid transporters. Metabolomic analyses show that these changes in transporters are associated with altered profiles of amino acids in the blood, kidney, and urine. Stable isotope glutamine tracing in primary tubule cells isolated from kidney cortices confirms that ATF4 regulates glutamine transport and metabolism. We suggest that even in the absence of additional stresses, such as kidney injury, ATF4 in the proximal tubules modulates both retention of specific nutrients and excretion of catabolic products like creatinine to maintain normal kidney function. KEY MESSAGES: Activating transcription factor 4 (ATF4) deletion changed more than 30% of genome-wide transcripts and corresponding proteins in the proximal tubules. One set of the profound changes occurred in amino acid transporters and Slc22 family transporters. Changes in transporters were accompanied by altered profiles of amino acids and wastes in the blood, kidney, and urine. ATF4 in the kidney proximal tubules plays a key role in regulating both the reabsorption of nutrients and the excretion of wastes.

  PublisherOA PDFDOI

• Deletion of the transcription factor ATF4 in a model of clear cell renal cell carcinoma

  Neoplasia · 2025-06-04 · 1 citations

  articleOpen accessSenior authorCorresponding

  Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer in adults. We generated TRAnsgenic of Cancer of the Kidney (TRACK) mice that express a triple-mutant (P402A, P564A, and N803A) human HIF1α construct specifically in their proximal tubule (PT) cells. We demonstrated that the elevated lipid content found in human ccRCCs is mimicked in these TRACK PT cells. Additionally, we reported that ATF4 (activating transcription factor 4), a transcription factor, and its target genes were highly expressed both in human ccRCCs and in TRACK PT cells. To delineate the functions of ATF4 in ccRCC we have now generated TRACK mice in which the ATF4 gene is specifically deleted in PT cells (GCREA∆T). Our genome-wide transcriptomics and proteomics studies show that expression of ∼20 % of mRNAs and proteins is significantly altered in GCREA∆T compared to TRACK kidney cortices. Gene set enrichment analyses (GSEAs) of mRNAs demonstrate that the fatty acid metabolism pathway is upregulated in TRACK vs WT and that, conversely, ATF4 deletion reduces mRNAs in the fatty acid metabolism pathway (e.g., ATP citrate lyase). Moreover, some transcripts elevated in human ccRCC are reduced in GCREA∆T vs. TRACK kidney cortices and cystic, pre-cancerous lesions are also reduced. Thus, ATF4 actions increase both lipid droplet accumulation in this ccRCC model and oncogenesis-related gene expression. These data suggest that ATF4 contributes to the formation of ccRCC tumors and may be a potential therapeutic target.

  PublisherDOI

• Retinoic acid receptor β deletion in podocytes causes kidney and liver dysfunction, modeling nephrotic syndrome

  Journal of Molecular Endocrinology · 2025-12-09

  articleOpen accessSenior author

  Differentially altered expression of transcripts of retinoic acid receptors α, β, γ (Rarα, β, γ), which mediate the actions of all-trans retinoic acid (RA), is observed in glomeruli of nephrotic syndrome (NS) patients vs normal individuals, with Rarβ reduced and both RARα and RARγ increased. Thus, we generated a mouse model (PCRB) with Rarβ specifically deleted in podocytes to define the glomerular actions of Rarβ. Rarβ deletion in PCRB mice results in podocyte loss, podocyte foot process effacement, glomerular basement membrane (GBM) thickening, reduced podocyte adhesion to the GBM, lipid accumulation in glomeruli, and hyperfiltration leading to albuminuria. Genome-wide transcriptomics and proteomics studies of glomeruli revealed that Rarβ deletion increased Mogat, Dgat, and Hmgcs mRNAs, which catalyze triglyceride and cholesterol synthesis, and Slc27a2 and Cd36, which mediate fatty acid uptake, recapitulating NS symptoms. Surprisingly, podocyte-specific Rarβ deletion also increased key mRNAs and proteins involved in fatty acid uptake and lipid biosynthesis in the liver, promoting steatohepatitis and systemic hyperlipidemia. These data indicate that Rarβ signaling in the kidney has a profound impact on both kidney and liver functions and suggest that Rarβ plays an important role in regulating kidney-liver crosstalk. PCRB mice may be a useful model of NS.

  PublisherDOI

• Exogenous BMI1 expression aggravates oral squamous cell carcinomas in tongue epithelia

  Neoplasia · 2025-02-25 · 1 citations

  articleOpen accessSenior authorCorresponding

  Oral squamous cell carcinoma (OSCC) is characterized by aggressiveness and a poor prognosis, in part because most patients are diagnosed during the later stages of the disease. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), part of polycomb repressive complex 1 (PRC1), is a key transcription factor overexpressed in OSCC. Although increased BMI1 has been linked to tumor formation in mouse models of the disease, the molecular mechanisms have not been elucidated. Here we used a transgenic mouse line (KrTB) that selectively overexpresses BMI1 in the tongue basal epithelial stem cells (SCs) to delineate BMI1 actions during oral tumorigenesis. By tumor pathological classification after 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis we detected more severe tumors in mice with ectopic BMI1 expression. Genome-wide transcriptomics indicated that mRNAs associated with human OSCC, including SOX9, HIF1A, MMP9, INHBB, and MYOF, were further increased by ectopic BMI1 expression in murine tongue epithelia. mRNAs encoding multiple metabolic targets, such as SLC2A1 (GLUT1), PKM, LDHA, and HK2, were also increased upon BMI1 overexpression in 4-NQO-treated tongue epithelia. Furthermore, we detected BMI1, SOX9, and GLUT1 proteins in the infiltrating cells of invasion fronts identified by markers of invasive SCCs. Finally, metabolomic data show that BMI1 overexpression in tongue epithelia promotes glycolysis during 4-NQO-induced carcinogenesis. Thus, our data demonstrate that BMI1 causes OSCC cells to alter cell metabolism, as changes in many of these transcripts are linked to increased glycolysis and metabolic reprograming that occurs during carcinogenesis.

  PublisherDOI

• Key Early Changes in Oral Squamous Cell Carcinogenesis Are Accelerated by Ectopic BMI1 Expression

  Cancer Research Communications · 2025-12-12

  articleOpen accessSenior author

  Although 5-year relative survival rates for oral squamous cell carcinoma (OSCC) have moderately increased in the last 30 years, most patients are diagnosed during the later stages of the disease. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a biomarker of OSCC that is increased in epithelial basal stem cells (SC) of premalignant oral lesions. However, the molecular functions of BMI1 in early-stage OSCC have not been fully elucidated. In this study, we used a transgenic mouse line (KrTB) that overexpresses BMI1 in the tongue epithelial SCs to delineate BMI1 actions during these early stages. We observed more oncogenic changes in mice with ectopic BMI1 expression after only a short, 4-week treatment with the carcinogen 4-nitroquinoline 1-oxide (4-NQO). For example, we detected increased proliferation, oxidative stress, and expression of multiple transcripts and proteins linked to human OSCCs in murine tongue epithelia with high, ectopic BMI1 expression. Furthermore, increases in mRNAs encoding multiple metabolic targets, such as SLC16A3, PKM, and GPI1, were greater upon BMI1 overexpression with 4 weeks of 4-NQO treatment. In a human OSCC model (SCC-25 cell line) in which we deleted the BMI1 gene, we observed decreases in proliferation, oxidative stress, and expression of the glycolysis-associated protein GLUT1. Thus, BMI1 expression leads to increases in key features of early-stage, carcinogen-induced tumorigenesis, including metabolic reprogramming. Consequently, limiting BMI1 could be a potential target for cancer prevention approaches that merits further consideration and additional functional studies. SIGNIFICANCE: Most OSCC diagnoses occur in advanced stages. Our data indicate that BMI1 overexpression, as detected in premalignant oral lesions, increases proliferation, oxidative stress, and expression of human OSCC-associated targets in our murine model after a short, 4-week carcinogen treatment. Thus, BMI1 could be a potential target for cancer prevention approaches.

  PublisherOA PDFDOI

Recent grants

• Cancer Pharmacology

  NIH · $532k · 1994–2020

• NIH Grant R01HD024319

  NIH · $2.2M · 1999

• NIH Grant R01DE010389

  NIH · $6.5M · 2016

• Cancer Pharmacology

  NIH · $12.5M · 1994–2026

• NIH Grant R01AA018332

  NIH · $2.1M · 2016

Frequent coauthors

• David M. Nanus

  New York Hospital Queens

  141 shared

• Nigel P. Mongan

  University of Nottingham

  125 shared

• Xiao‐Han Tang

  Second Xiangya Hospital of Central South University

  116 shared

• Kristian B. Laursen

  Cornell University

  98 shared

• Francesca Khani

  Weill Cornell Medicine

  95 shared

• Johannes C. van der Mijn

  The Netherlands Cancer Institute

  81 shared

• Steven E. Trasino

  City University of New York

  77 shared

• Qiuying Chen

  First Affiliated Hospital of Jinan University

  71 shared

Labs

• Gudas LabPI