About

Ramesh Ganju, PhD, is a Professor and Vice Chair of the Department of Pathology at The Ohio State University, a position he has held since 2007. His laboratory primarily focuses on elucidating mechanisms that regulate tumor growth and metastasis, with a particular emphasis on developing immune-based therapies against solid tumors. Dr. Ganju has made significant contributions to the understanding of T-cell receptor (TCR) engineering, demonstrating the feasibility of producing soluble, antigen-binding TCR fragments through protein engineering in E. coli, and identifying key residues involved in antigen recognition. His research extends to the analysis of signaling pathways involved in tumor progression, including the roles of molecules such as RAFTK, CD45, and chemokine receptors like CXCR4. He has identified novel biomarkers and signaling molecules that regulate breast cancer growth and metastasis, especially in triple-negative breast cancer, and has developed transgenic and knockout mouse models to study tumor microenvironment interactions. Dr. Ganju's work also explores the tumor microenvironment's influence on cancer progression, including the roles of tumor-associated macrophages and pro-inflammatory molecules such as RAGE and S100A7. Additionally, his laboratory investigates small molecular weight anti-inflammatory compounds, including synthetic cannabinoids, for their potential to inhibit lung and breast cancer growth and metastasis. He has been continuously funded by NIH for over 22 years and has collaborated extensively with other researchers, mentoring numerous students and fellows.

Research topics

• Internal medicine
• Cancer research
• Medicine
• Biology
• Immunology
• Genetics
• Endocrinology

Selected publications

• Immunotherapy in Small Cell Lung Cancer: Advances, Barriers, and Emerging Strategies

  Onco · 2026-02-05

  articleOpen accessSenior author

  Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine disease marked by rapid growth, early metastatic spread, and poor outcomes. The addition of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis to first-line chemotherapy has recently reshaped the treatment landscape for extensive-stage SCLC (ES-SCLC); however, the resulting survival gains remain modest compared with non-small lung cancer (NSCLC). This review explores the molecular features of the SCLC immune landscape that contribute to its predominantly “cold” tumor phenotype, including low MHC class I expression, T-cell exhaustion, and a profoundly immunosuppressive tumor microenvironment (TME). We summarize key clinical findings from landmark trials and examine mechanisms of both primary and acquired resistance against ICIs in SCLC. In addition, we have reviewed the growing role of precision medicine in SCLC, including molecular subtyping (SCLC-A, -N, -P, and -I) and the development of next-generation immunotherapies such as bispecific T-cell engagers (BiTEs), B7-H3, targeted therapy, and antibody–drug conjugates. By combining existing clinical evidence with new molecular insights, this review article presents strategies to overcome the existing therapeutic plateau and enhance personalized immunotherapy approaches in SCLC.

  PublisherOA PDFDOI

• Estrogen Signaling During Abrupt Involution and Long-Term Metabolic Signature Similar to Estrogen Receptor-Negative Breast Cancer

  International Journal of Molecular Sciences · 2026-02-18

  articleOpen access

  Epidemiological data link a lack of breastfeeding with an increased risk of breast cancer. Breast tissue remodels after pregnancy through involution. Long-term breastfeeding results in gradual involution (GI), and a lack of breastfeeding leads to abrupt involution (AI). AI causes increased mammary gland estrogen signaling, causing adipocyte redifferentiation through neutrophil infiltration. Adipocyte differences and metabolic implications of involution have not been explored between AI and GI. As breast cancer is characterized as highly metabolic, we explored how adipocyte differences and metabolism during involution may support breast cancer risk. FVB/n was randomized to AI/GI and standardized to 6 pups on day 0/birth. AI mice had pups removed on day 7. GI mice had 3 pups removed on days 28 and 31. Mammary glands were harvested at 28, 56, and 120 days. A subset of AI mice were given tamoxifen for 21 days. Day 28 AI glands had upregulation of estrogen signaling, neutrophil degranulation, and glucose metabolism and downregulation of adipogenesis and glycolysis compared to Day 56 GI. Day 120 AI glands had downregulation of oxidative phosphorylation and upregulation of mitochondrial dysfunction similar to estrogen receptor-negative (ER-) pregnancy-associated breast cancer (PABC). AI with tamoxifen resulted in a similar metabolic phenotype to GI. Early metabolic phenotypes in AI and GI glands may be related to estrogen signaling. AI long-term transcriptional metabolic effects were similar to breast cancer.

  PublisherOA PDFDOI

• Abstract 7463: Targeting S100A7/RAGE-driven Stat3/Serpin-E1 signaling for immunotherapy in metastatic breast cancer

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive type that lacks targeted therapies, with immunosuppressive variants resistant to checkpoint blockade. Elevated S100A7 expression is reported in these immune-ignored, anti-PD1-refractory tumors; yet S100A7 mechanisms, which shape the immune tumor microenvironment (iTME), remain unclear. Here, we investigated how S100A7 activates the RAGE/Stat3 axis to induce Serpin-E1, reshaping the iTME, and assessed therapeutic potential in immunosuppressive TNBC. Method: Expressions of S100A7, RAGE, Stat3, and Serpin-E1 were analyzed in TNBC cells by Western blotting, cytokine arrays, and ELISA. Functional assays evaluated the impact of S100A7 overexpression (OE) or knockdown (KD) and pharmacologic inhibition of RAGE and Stat3, alone or combined, on viability, migration, and colony formation. Pre-clinical models, including doxycycline (DOX)-inducible mammary gland-specific S100A7-OE bitransgenic mice treated with RAGE and Stat3 inhibitors ± Serpin-E1 neutralizing antibody (nAb) were utilized for in-vivo studies. Multi-color flow cytometry determined macrophage polarization and T-cell activation. CD4/CD8 depletion assays and in-silico analyses evaluated T-cell dependency and prognostic significance. Results: S100A7 upregulation enhanced phosphorylation of Stat3 (Ser727) and Serpin-E1 expression, whereas its downregulation suppressed pStat3/Serpin-E1. Dual inhibition of RAGE and Stat3 produced synergistic suppression of TNBC cell viability, migration, and colony formation and markedly inhibited downstream pStat3 signaling. Mechanistic studies revealed that S100A7/RAGE signaling activates Stat3, which binds to the Serpin-E1 promoter and enhances its transcription. In-vitro assays demonstrated a potential role for Serpin-E1 in modulating macrophage polarization. Next, in-vivo treatment of RAGE and Stat3 inhibitors ± Serpin E1 nAb led to significant reductions in primary tumor growth and distant metastasis in female NSG mice. Significantly decreased tumor burden in S100A7-OE mice treated with the combination of RAGE/Stat3 inhibitors was observed compared to alone treatment groups alone. Additional immune profiling within tumor tissues revealed a significant abundance of antitumor iNOS and MHCIIhigh TAMs and increased activation of CD4+ and CD8+ T cells with elevated effector markers in combinatorial treatment compared to a single regimen. These effects were abrogated by CD4/CD8 depletion. Clinically, high co-expression of S100A7 and Serpin-E1 correlated with poorer outcomes, particularly in basal and immunomodulatory TNBC subtypes. Conclusions: This study identifies the S100A7/RAGE/Stat3/Serpin-E1 axis as a key regulator of tumor growth and iTME suppression in TNBC and its potential for a targeted therapeutic strategy for immune-ignored TNBC subtypes. Citation Format: Pratyusha Ghanta, Ajeet K. Verma, Cho-Hao Lin, Manish Charan, Ganesh R. Koshre, Tanisha Mukherjee, Wayne O. Miles, Sanjay Mishra, Ramesh Ganju, . Targeting S100A7/RAGE-driven Stat3/Serpin-E1 signaling for immunotherapy in metastatic breast cancer [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 7463.

  PublisherDOI

• Therapeutic targeting of RAGE/STAT3 signaling abrogates S100A7-driven breast tumorigenicity and immune suppression

  Breast Cancer Research · 2026-04-29

  articleOpen accessSenior author

  Abstract Metastatic breast cancer, particularly triple-negative breast cancer (TNBC), remains a major clinical challenge due to its aggressive behavior and limited therapeutic options. The molecular pathways that drive tumor progression while simultaneously promoting immune evasion are not well defined. Here, we identify S100A7/RAGE signaling as a central oncogenic and immunomodulatory axis that drives TNBC tumorigenicity, metastasis, and immune suppression. In this study, we have shown that S100A7/RAGE signaling plays a vital role in driving invasive TNBC tumorigenicity by activating Stat3 and elevating Serpin-E1 expression. Furthermore, we revealed that combinatorial treatment of Stat3 and RAGE inhibitors synergistically inhibits the tumorigenicity of S100A7-expressing TNBC cells in-vitro by suppressing AKT/MAPK signaling and mitigates the tumor burden, especially distant metastasis in-vivo using TNBC cell lines and a conditional mammary gland-specific S100A7 overexpression bitransgenic mouse model. Moreover, our study also shed light on the dynamic interplay between the S100A7/RAGE/Stat3 signaling pathway and immune cell infiltration within the tumor microenvironment. Remarkably, our findings underscored the potential of combined inhibition to enhance anti-tumor immune responses, fostering the infiltration of anti-tumor MHCII high and iNOS + macrophages and activated effector CD8 + tumor-infiltrating T cells. Moreover, CD8 + T cells depletion abrogates the therapeutic benefits of RAGE/Stat3 inhibition by restoring the tumor growth in S100A7 overexpression mice. Importantly, we discovered that S100A7/RAGE signaling modulates anti-tumor macrophage phenotypes by regulating Serpin-E1 expression on TNBC cells. S100A7 regulates Serpin-E1 gene expression by enhancing the direct binding of pStat3 (Ser727) to its promoter. Notably, neutralization of Serpin-E1 in combination with RAGE and Stat3 inhibition increased iNOS expression in macrophages in-vitro and significantly enhanced overall anti-metastatic efficacy in-vivo. Importantly, we found that increased co-expression of S100A7 and Serpin-E1 correlated with worse prognoses in TNBC patients, whereas the presence of iNOS or MHCII genes improved the overall prognosis, especially basal and immunomodulatory subtypes, which also underscores the clinical relevance of targeting these signaling molecules as a promising translational therapeutic strategy for TNBC. Overall, these findings provide new avenues for therapeutic interventions in metastatic TNBC. Graphical abstract

  PublisherDOI

• Psoriasin Confers Therapeutic Vulnerability to cPLA2 Inhibition via NHERF2/GSK3β Signaling in Triple-Negative Breast Cancer

  SSRN Electronic Journal · 2026-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Divergent paths of mammary gland involution: unveiling the cellular dynamics in abruptly and gradually involuted mouse models

  Breast Cancer Research · 2025-01-03 · 9 citations

  articleOpen access

  BACKGROUND: Epidemiological studies associate an increase in breast cancer risk, particularly triple-negative breast cancer (TNBC), with lack of breastfeeding. This is more prevalent in African American women, with significantly lower rate of breastfeeding compared to Caucasian women. Prolonged breastfeeding leads to gradual involution (GI), whereas short-term or lack of breastfeeding leads to abrupt involution (AI) of the breast. Our previous study utilizing a murine model demonstrated precancerous changes, specifically hyperplasia, a non-obligate precursor of breast cancer in the mammary glands of AI mice. Here we investigated mechanisms during early events of AI that prompts precancerous changes in mouse mammary glands. METHODS: Uniparous FVB/N mice were randomized to AI and GI on postpartum day 7 when all pups were removed from AI dams. GI dams were allowed to nurse the pups till day 31. Cell death kinetics and gene expression were assessed by TUNEL assay and qPCR respectively. Immune cell changes were investigated by flow cytometry, cytokine array and multiplex immunofluorescence. 3D-organoid cultures were used for in vitro assay of luminal progenitor cells. RESULTS: AI results in rapid cell death, DNA repair response, and immunosuppressive myeloid cells infiltration, leading to a chronically inflamed microenvironment. GI elicits a more controlled immune response and extended cell death. At the peak of cell death, AI glands harbored more immunosuppressive myeloid-derived suppressor cells (MDSCs) and CD206 + M2-like macrophages, known to promote oncogenic events, compared to GI glands. AI glands exhibit an enrichment of CCL9-producing MDSCs and CD206 + M2-like macrophages that promote expansion of ELF5 + /ERα- luminal cells, both in vitro and in vivo. Multiplex imaging of AI glands demonstrated an increase in ELF5 + /WNT5a + luminal cells alongside a reduction in the ELF5 + /ERα + population when involution appeared histologically complete. A significantly higher number of CD206 + cells in post involution AI gland attests to a chronically inflamed state induced by AI. CONCLUSIONS: Our findings reveal significant disparities between AI and GI gland dynamics at the early phase of involution. CCL9, secreted by immune cells at the peak of cell death promotes expansion of Elf5 + /ERα- luminal progenitor cells, the putative precursors of TNBC connecting early events of AI with increased breast cancer risk.

  PublisherOA PDFDOI

• Abstract P1-03-06: Abrupt Involution Leads to Long-Term Mitochondrial Dysfunction and Metabolic Shift – Increasing Risk of Breast Cancer

  Clinical Cancer Research · 2025-06-13

  article

  Abstract Epidemiological data links higher parity and lack of breastfeeding with increased risk of breast cancer, specifically triple negative breast cancer (TNBC). TNBC is the aggressive hormone receptor and HER2 negative subtype associated with higher mortality rate1. Following pregnancy and lactation, breast remodels to near pre-pregnancy stage through apoptotic cell death and adipocyte repopulation process2. Long-term breastfeeding and gradual weaning of an infant leads to gradual involution (GI) of the breast, while lack of or abrupt discontinuation of breastfeeding after birth leads to abrupt involution (AI), when rapid and massive cell death takes place2. Our studies comparing GI vs. AI in a mouse model have shown several precancerous changes, such as increased collagen deposition, inflammation, and hyperplasia in the mammary gland of mice after AI2. While our preliminary data indicates metabolic shifts in the AI glands, the impact of AI on mammary gland metabolism and how this increases risk of breast cancer is yet to be elucidated. Objectives: Determine the impact of AI on metabolic changes within the mammary gland and decipher the underlying mechanism that could link AI to increased breast cancer risk. Methods: Eight-week-old FVB/n mice were paired for breeding. At partum (day 0), dams were randomized to AI or GI cohort, standardized to 6 pups per dam and housed individually. AI mice had pups removed on day 7 postpartum (ppm) to mimic short-term breastfeeding. For GI mice 3 pups each were removed on day 28 and 31 ppm to mimic gradual weaning. Mammary glands were harvested on day 28, 56, and 120 ppm to assess short-term, intermediate, and long-term effects of AI vs. GI. Total mammary gland RNA was subjected to global gene expression analysis using Affymetrix and analyzed Ingenuity pathway analysis software. Differentially expressed genes were validated by qPCR and western blot. Oxidative stress was measured via MitoSox and H2CDFDA using Flow Cytometry. Whole mammary glands were subjected to untargeted metabolomics and lipidomics. Results: On day 28 ppm, AI glands had marked upregulation of oxidative phosphorylation, ATP synthesis, and mitochondrial fatty acid b-oxidation compared to GI glands. AI glands had significantly higher levels of mitochondrial oxidative stress and enrichment of oxidized glycerophospholipids. On day 56 ppm, AI glands were metabolically comparable to GI glands. However, AI glands had an upregulation of genes related to fatty acid synthesis (PPARg, ACLY, Chrebp, GLUT4 and SLC25A1) and mitochondrial biogenesis (PGC1a). Interestingly, on day 120 ppm, AI glands showed significant downregulation of oxidative phosphorylation, ATP synthesis, glucose metabolism, and marked upregulation of mitochondria dysfunction. Amyloid precursor protein (APP) associated with mitochondria dysfunction and downregulation of energy metabolism, was found to be elevated in AI vs. GI glands on day 120 ppm. Conclusion: AI of the mammary gland leads to metabolic changes over time that disrupt mitochondrial function. Multiple studies have associated high levels of APP in human breast tumors and breast cancer cell lines with disruption of mitochondria function, enhanced cell proliferation, metastasis and invasion. Increased expression of APP in AI mammary glands suggests a key role of this protein in mitochondrial and metabolic dysfunction induced by AI. Further investigation is underway to decipher the role of APP in AI induced changes. Significance: For the first time, this study demonstrates a metabolic shift in the mammary gland caused by AI. Targeting one or more key players in this metabolic deregulation could provide options for lowering breast cancer risk in women who are unable to breast feed. *Funding NCI RO1 – CA237185 PI-Ramaswamy/Ganju Citation Format: Kate Ormiston, Neelam Shinde, Gautam Sarathy, Allen Zhang, Morgan Bauer, Rajni Kant Shukla, Sara Alsammerai, Annapurna Gupta, Djawed Bennouna, Xiaoli Zhang, Rachel Kopec, Eswar Shankar, Ramesh Ganju, Kristin I. Stanford, Sarmila Majumder, Bhuvaneswari Ramaswamy. Abrupt Involution Leads to Long-Term Mitochondrial Dysfunction and Metabolic Shift – Increasing Risk of Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-03-06.

  PublisherDOI

• Sulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP

  Cancer Biology & Therapy · 2025-03-26 · 3 citations

  articleOpen access

  The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functional group essential for ATPase inhibition. Consequently, we propose that TNBC cell death and eATP release induced by chemotherapy would be intensified by SULF2 inhibitors. We examined eATP and cell viability in paclitaxel-treated TNBC and nontumorigenic immortal mammary epithelial MCF-10A cells in the presence of OKN-007, a selective SULF2 inhibitor, and/or heparan sodium sulfate. Furthermore, sulfatase 1 (SULF1) and SULF2 protein expressions were ascertained. We found that the expression of SULF2 was greater in TNBC cell lines when compared to MCF-10A cells. The release of eATP and loss of TNBC cell viability induced by chemotherapy was enhanced by OKN-007. The co-treatment of chemotherapy and OKN-007 also attenuated cancer-initiating cells. This data implies that the combination of SULF2 inhibitors with chemotherapy augments eATP and decreases cell viability of TNBC greater than chemotherapy alone.

  PublisherOA PDFDOI

• Erratum: Reciprocal regulation of microRNA-122 and c-Myc in hepatocellular cancer: Role of E2F1 and transcription factor dimerization partner 2

  Hepatology · 2025-04-03

  erratum
  PublisherDOI

• Abstract P1-07-24: Induced Electric Fields Restrict Breast Cancer progression and metastasis via Immune Microenvironment Regulation

  Clinical Cancer Research · 2025-06-13

  article

  Abstract Breast cancer is the leading cause of cancer-related deaths in women across the globe. TNBC is a significant cause of mortality among breast cancer subtypes due to its aggressive nature and limited treatment options compared to other subtypes. Therefore, the development of safer and more effective therapies is urgently required. We found that alternating (100 kHz), and low intensity (<1 mV/cm) induced electric field (iEF) inhibits tumor growth and metastasis in an orthotopic TNBC model. Non-contact iEF treatment can be delivered safely and non-invasively in vivo via a hollow, rectangular solenoid coil. Furthermore, we discovered that iEF treatment significantly enhanced the anti-tumor immune responses. In particular, it enhances anti-tumor immune activity in both the primary tumor and distant lung metastases. Notably, iEF treatment decreases the exhaustion of CD8+ T cells and reduces the infiltration of immunosuppressive immune cells in the tumor microenvironment, creating a less hospitable environment for cancer progression. Moreover, iEF treatment reduces the formation of lung metastases by promoting the enrichment of CD8+ T cells while suppressing immunosuppressive Gr1+ neutrophils in the lung microenvironment. We further observed that iEFs inhibit the ability of cancer cells to undergo epithelial-to-mesenchymal transition, thereby decreasing their metastatic potential. Furthermore, these findings suggest that iEFs could be a promising strategy to enhance overall anti-tumor immunity against aggressive and metastatic breast cancers. Taken together, the utilization of iEF technology could revolutionize current treatment paradigms for metastatic breast cancer. Citation Format: Manish Charan, Travis Jones, Nandini Acharya, Vish V. Subramaniam, Ramesh Ganju, Jonathan W Song. Induced Electric Fields Restrict Breast Cancer progression and metastasis via Immune Microenvironment Regulation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-07-24.

  PublisherDOI

Recent grants

• NIH Grant R01AI049140

  NIH · $1.5M · 2007

• NIH Grant R21AI091420

  NIH · $419k · 2014

• NIH Grant R29CA076950

  NIH · $633k · 2002

• Addressing cancer disparity through defining the molecular link between breast feeding and triple negative breast cancer

  NIH · $2.2M · 2019–2025

• NIH Grant R01CA153490

  NIH · $1.2M · 2016

Frequent coauthors

• Mohd W. Nasser

  University of Nebraska Medical Center

  126 shared

• Jerome E. Groopman

  108 shared

• Dinesh K. Ahirwar

  80 shared

• Zahida Qamri

  71 shared

• Konstantin Shilo

  The Ohio State University

  61 shared

• Anju Preet

  Georgetown University

  56 shared

• Xianghong Zou

  43 shared

• Shalom Avraham

  Beth Israel Deaconess Medical Center

  42 shared

Labs

• AI4PathPI

  From Pixels to Prognosis: AI in Action!

Education

• B.S.

  Panjab University

  1979

• M.S.

  Panjab University

  1980

• Ph.D.

  Indian Institute of Science

  1985

Awards & honors

• Scott Endowed Professor, Vice Chair of Experimental Patholog…