About

Professor Manish Bais, DVM, PhD, is the Principal Investigator of the Bais Research Group at the Department of Translational Dental Medicine, Boston University. His research group focuses on molecular and epigenetic mechanisms underlying oral cancer, osteoarthritis, and cartilage regeneration. The lab investigates the role of LSD1-induced signaling mechanisms in sensitizing oral cancer to chemotherapy and immunotherapy, as well as the genetic and epigenetic regulation of LOXL2 in temporomandibular joint (TMJ) and knee osteoarthritis. Professor Bais's research has contributed to understanding the molecular pathways involved in orofacial and skeletal biology, with his students and postdoctoral associates producing award-winning research and publications in these areas.

Research topics

• Medicine
• Internal medicine
• Anatomy
• Pathology
• Chemistry
• Biochemistry
• Cancer research

Selected publications

• Abstract 4632: LSD1 inhibition enhances radiotherapy efficacy in OSCC by attenuating SUMOylation and activating NK cells

  Cancer Research · 2026-04-03

  articleOpen accessSenior author

  Abstract Background: Oral squamous cell carcinoma (OSCC) is a prevalent and deadly cancer, with limited treatment success using radiation therapy (RT) alone. This study investigated the role of lysine-specific demethylase 1 (LSD1) in promoting oncogenic signaling, resistance to RT, and immunosuppression in OSCC. We hypothesized that targeting LSD1-specific mechanisms, in combination with RT, could inhibit OSCC growth and immune evasion. Methods: We employed a 4NQO-treated progressive mouse OSCC model to identify the molecular and cellular changes during radiotherapy and LSD1 inhibition (with SP2509) in combination with radiation. To identify these changes, we used RNA-seq for pathway-related changes, flow cytometry for immune regulation, and in vitro cell culture techniques for ChIP, qRT-PCR, and pathway validation. Finally, we treated feline spontaneous OSCC with a combination of SP2509 and radiation to test its efficacy. Results: RT combined with the LSD1 inhibitor SP2509 promoted the infiltration of natural killer (NK) cells and dendritic cell (DC)-mediated antitumor immunity in mouse OSCC preneoplasia. Feline OSCC treated with an LSD1 inhibitor and RT showed reduced tumor growth. In vitro studies have demonstrated that combination therapy induces the activation of IFNγ+ CD8+ T cells and NK cells. RNA sequencing showed that the combination therapy attenuated the cell cycle and CDK-related pathways. Clinical OSCC samples treated with RT exhibited inhibition of CD8+ T cells, while the combination of an LSD1 inhibitor and RT recovered CD8+ T cell proliferation with a significant increase in NK cell population in mouse OSCC and peripheral blood mononuclear cells co-cultured with human OSCC cells (HSC3). It was also observed that LSD1 inhibition in OSCC, both in vivo and in vitro, attenuated SUMOylation pathways and downregulated the SUMO1 gene while upregulating NKG2DL-related genes such as MICB in humans and their mouse analog RAEγ. Using ChIP-qPCR, we observed that LSD1 inhibition increased H3K9me2 methylation at the SUMO1 gene locus and decreased H3K4me2 methylation. LSD1 inhibition in combination with radiotherapy in feline OSCC attenuates cancer growth. Conclusion: SP2509 treatment enhances the efficacy of radiation therapy by inhibiting SUMOylation pathways, which increases NK cells by NKG2DL-NKG2D axis activation, thereby inducing anti-tumor immunity. Citation Format: Chumki Choudhury, Amit Kumar Chakraborty, Rajnikant Raut, Marilia Takada, Bikash Sahay, Minh-Tam Truong, Daniel L. Gustafson, Jenna Burton, Manish V. Bais. LSD1 inhibition enhances radiotherapy efficacy in OSCC by attenuating SUMOylation and activating NK cells [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 4632.

  PublisherDOI

• Abstract 5577: LSD1 inhibition remodels the tumor microenvironment to enhance anti-PD1 immunotherapy in HNSCC

  Cancer Research · 2026-04-03

  articleOpen accessSenior author

  Abstract Background: The histone demethylase LSD1 (KDM1A), an epigenetic regulator implicated in tumor progression and immune suppression. Programmed cell death protein-1 (PD-1/CD279) marks exhausted CD8+ T cells and binds PD-L1 (CD274) in the tumor epithelium. Anti-PD-1 therapy has limited success in head and neck squamous cell carcinoma (HNSCC). We hypothesized that LSD1 inhibitor (SP2509), due to its specific mechanisms, shows superior anti-cancer activity in combination with anti-PD1 therapy. Methods: We assessed SP2509’s impact on the tumor microenvironment (TME) in a syngeneic 4MOSC1 oral squamous cell carcinoma (OSCC) model and 4NQO-induced progressive OSCC model. Anti-PD-1 monotherapy and anti-PD-1-SP2509 combination therapy were tested in a 4NQO model. Multiple methods like immunostaining, qRT-PCR, flowcytometry were employed to test the hypothesis. Ovalbumin overexpression assay followed by flowcytometry was used to determine the antigen presentation in every groups. ChIP-qPCR was used to determine the H3K4 and H3K9 methylation change status on HLA-A, HLA-B and PD-L1 gene locus. Public RNA-seq data (GSE153383) were analyzed to examine immune cell responses to anti-PD-1 and compared with our findings. Results: SP2509 increased immune cell infiltration, including CD8+ T cells, and reduced the frequency of PD-L1+ epithelial tumor cells in both 4MOSC1 and 4NQO models. Anti-PD-1 monotherapy expanded CD8+ T cells but did not alter PD-L1 + epithelial cells. Each treatment alone enhanced CD8+ T-cell IFN-γ production, consistent with the GSE153383 analysis showing elevated T-cell infiltration and IFN-γ in anti-PD-1 treated samples. Furthermore, we observed a significant increase in antigen presentation in anti-PD-1 and SP2509 combination group with ovalbumin assay. The combination regimen produced greater immune infiltration, particularly CD8+ T-cells with higher IFN-γ levels, a significant reduction in PD-L1+ epithelial cells, and more pronounced tumor regression than anti-PD-1 alone was observed in vivo. ChIP-qPCR results shows increase in H3K4me2 in HLA-A and HLA-B gene locus while H3K9me2 increase in PD-L1 gene locus was observed after SP2509 treatment. We also observed DC activation in SP2509 alona and in combination groups and absent in only anti-PD1 treatment group. Conclusions: Targeting LSD1 with SP2509 enhances the anti-PD-1 efficacy in HNSCC by modulating the TME, augmenting CD8+ T-cell-mediated antitumor immunity and antigen presentation via MHC class I activation, and reducing tumor PD-L1 expression, ultimately leading to a reduction in HNSCC growth. Citation Format: Amit Kumar Chakraborty, Chumki Choudhury, Rajnikant Raut, Manish V. Bais. LSD1 inhibition remodels the tumor microenvironment to enhance anti-PD1 immunotherapy in HNSCC [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 5577.

  PublisherDOI

• LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-κB-induced chondrocyte apoptosis

  International Journal of Oral Science · 2026-02-04

  articleOpen accessSenior author

  Abstract Temporomandibular joint osteoarthritis (TMJ-OA) affects a significant proportion of the population worldwide. However, there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms. Lysyl Oxidase-Like-2 (LOXL2) promotes knee joint cartilage protection and is downregulated in a TMJ-OA animal model. We evaluated the role of LOXL2 in TMJ cartilage, its molecular mechanism, and gene networks using in vivo Loxl2 knockout mice ( Acan-Cre; Loxl2 flox/flox ) and ex vivo goat TMJ cartilage. Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b , Mmp9 , Mmp13 , Adamts4 , and Adamts5 , but reduces the levels of aggrecan and proteoglycan. Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response, TNFA signaling via NF-κB, extracellular matrix (ECM), and collagen degradation pathway network. Conversely, LOXL2 treatment reduces interleukin-1 beta (IL-1β)-induced expression of Mmp13 , protects mitochondrial function, and ECM from degeneration. Importantly, LOXL2 attenuates IL-1β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2 (encodes COX2). Taken together, Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation, mitochondrial dysfunction, chondrocyte apoptosis, and inflammatory gene expression, whereas LOXL2 treatment mitigate these effects.

  PublisherOA PDFDOI

• Additional file 2 of Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer

  Figshare · 2025-01-01

  datasetOpen access

  Tabular spreadsheet file containing both table of differential gene expression results comparing ICG-001 treatment (n = 3) versus DMSO (vehicle) control (n = 3) in HSC-3 and CAL27 OSCC cell lines, as well as the ICG-001 treatment gene expression signatures derived thereof (see manuscript “Methods”). (XLSX 4246 kb)

  PublisherDOI

• Modified Medial Meniscectomy (MMM) Model to Assess Post-Traumatic Knee Osteoarthritis in Mouse

  Osteology · 2025-08-18 · 1 citations

  articleOpen access1st authorCorresponding

  Background/Objectives: Mechanical, physiological, and biochemical changes contribute to post-traumatic osteoarthritis (PTOA). Specific mouse models that are highly reproducible, less invasive, and easy to use are lacking. This limitation hinders the progress of PTOA-related studies on therapeutic applications. The goal of the study was to establish a methodologically innovative, efficient, and less technically challenging surgical model for PTOA. Methods: We developed a modified medial meniscectomy (MMM) model demonstrating high reproducibility and applicability. The MMM model features distinct differences in the execution of transection of the medial meniscus on the lateral side and includes a smaller incision, which enhances reproducibility and is beneficial for studying pain, structure, and function. Results: One month after the MMM surgery, the mice showed increased sensitivity to pain and decreased biomechanical abilities, such as shorter running times and distances. This was further supported by higher Osteoarthritis Research Society International (OARSI) histology scores, a standardized system for determining the severity and extent of OA in cartilage. Additionally, transcriptomic analysis showed an elevated enrichment of immune activity and bone tissue formation gene sets in the knee joint. Conclusions: Overall, functional studies and transcriptomic analyses suggested that the MMM model can be utilized for future biomechanistic and therapeutic applications and could serve as a new resource for studying PTOA.

  PublisherOA PDFDOI

• LSD1 inhibition corrects dysregulated MHC-I and dendritic cells activation through IFNγ-CXCL9-CXCR3 axis to promote antitumor immunity in HNSCC

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-17 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Poor infiltration of CD8+ T cells and dysregulated MHC-I confer resistance to anticancer clinical therapies. This study aimed to elucidate the mechanisms of lysine-specific demethylase 1 (LSD1, encoded by KDM1A gene) in antitumor immunity in Head and Neck Squamous cell carcinoma (HNSCC). LSD1 inhibition in syngeneic and chronic tobacco carcinogen-induced HNSCC mice recruited activated dendritic cells (DCs), CD4+ and CD8+ T cells, enriched interferon-gamma (IFNγ) in T cells, CXCL9 in DCs, and CXCR3 in T cells, as evaluated using flow cytometry and single-cell RNA-seq analysis. Humanized HNSCC mice and TCGA data validated the inverse correlation of KDM1A with DC markers, CD8+ T cells, and their activating chemokines. Kdm1a knockout in mouse HNSCC and LSD1 inhibitor treatment to co-culture of human HNSCC cells with human peripheral blood mononuclear cells (PBMCs) resulted in MHC-I upregulation in cancer cells for efficient antigen presentation in tumors. Overall, LSD1 inhibition in tumor cells upregulates MHC class I and induces DCs to produce CXCL9, which in turn activates CD8+ T cells through the CXCL9-CXCR3 axis to produce IFNγ. Finally, we identified a novel mechanism by which LSD1 inhibition promotes the activation of H3K4me2 and its direct interaction with MHC-I to induce antitumor immunity. This may have implications in poorly immunogenic and immunotherapy-resistant cancers. Statement of Significance LSD1-mediated unique mechanisms have impact on epigenetic therapy, MHC-I resistant HNSCC therapies, and poor CD8+ and dendritic cell infilterated tumors.

  PublisherOA PDFDOI

• Additional file 3 of Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer

  Figshare · 2025-01-01

  datasetOpen access

  Tabular ranked gene list file (viewable in Excel) pertaining to differential gene expression testing comparing siRNA-mediated knockdown of β-catenin versus scrambled siRNA control in HSC-3 cells used for GSEA. Fields indicate gene symbol and t test statistic of differential expression, respectively, used as input to the pre-ranked GSEA tool. (TXT 289 kb)

  PublisherDOI

• LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-κβ-Induced Chondrocyte Apoptosis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-13

  preprintOpen accessSenior authorCorresponding

  Abstract Temporomandibular joint osteoarthritis (TMJ-OA) affects a significant proportion of the population worldwide. However, there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms. Lysyl Oxidase Like-2 (LOXL2) promotes knee joint cartilage protection, and it is downregulated in TMJ-OA animal model. We evaluated the role of LOXL2 in TMJ cartilage, its molecular mechanism and gene networks using in vivo Loxl2 knockout mice ( Acan-Cre; Loxl2 flox/flox ) and ex vivo goat TMJ cartilage. Our results show that Loxl2 knockout in mice cartilage upregulates Il1b, Mmp9, Mmp13, Adamts4 , and Adamts5 , whereas it reduces the levels of aggrecan and proteoglycan. Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response, TNFA signaling via NF-kB, extracellular matrix (ECM), and collagen degradation pathway network. Conversely, LOXL2 treatment reduces interleukin-1 beta (IL-1β)-induced expression of Mmp13 , protects mitochondrial function and ECM from degeneration. Importantly, LOXL2 attenuates IL-1β-induced chondrocyte apoptosis via phosphorylation of NF-κB and expression of pain-related gene PTGS2 (encodes COX2). Taken together, Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation, mitochondrial dysfunction, chondrocyte apoptosis, and inflammatory gene expression, whereas LOXL2 treatment mitigates these effects. Graphical Abstract

  PublisherOA PDFDOI

• The unique molecular signature of TMJ as compared to the knee, demonstrates its susceptibility to osteoarthritis

  Journal of Oral Biosciences · 2025-07-16 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Dietary Serine Restriction Impacts H3K27 and H3K4 Methyl Epigenomes to Impede Head and Neck Cancer Cell Plasticity and Tumor Growth

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-22 · 1 citations

  preprintOpen access

  Head and neck cancer with its major subsite, oral squamous cell carcinoma (OSCC), is a devastating malignancy with limited treatment options. Given that recent advances in nutritional interventions have been recognized as potential strategies for targeting cancer, we investigated the role of dietary serine restriction in OSCC cell plasticity. Utilizing multiple human OSCC-derived cell lines and an orthotopic syngeneic mouse model of OSCC, we interrogated the impact of serine deprivation on this malignancy through biochemical assays, transcriptomic analyses, and CUT&RUN sequencing, as well as impact on tumor growth and its immune environment. We report that human OSCC cells behaved like serine auxotrophs, depending on exogenous serine for growth and maintenance of plastic cell states. We show that dietary restriction of serine induced endogenous serine synthesis and generated alpha-ketoglutarate (αKG), a co-substrate for JMJD3 nuclear dioxygenase, which demethylates H3K27me3 and de-represses differentiation genes. This was accompanied by the reduction of H3K4me3 at stemness and epithelial-to-mesenchymal transition (EMT) genes caused. Likewise, dietary serine restriction inhibited orthotopic OSCC isograft growth in mice concomitant with downregulation of H3K27me3 and increased immune infiltration in the tumor periphery. Collectively, our study provides new insights into the epigenetic etiology of OSCC that reveals the interplay between serine metabolism and epigenetic molecular mechanisms driving OSCC cell plasticity and tumorigenesis. The dependence of OSCC cells on exogenous serine to maintain plastic cell states offers a unique opportunity to utilize a non-toxic dietary serine restriction as an intervention treatment either alone or in combination with other therapies for OSCC patients.

  PublisherOA PDFDOI

Recent grants

• Epigenetic targeting of LSD1 for OSCC Therapy

  NIH · $454k · 2018–2021

• LOXL2 in Temporomandibular Joint Osteoarthritis

  NIH · $246k · 2015–2018

Frequent coauthors

• Nathan A. Wigner

  University of Pennsylvania

  51 shared

• Megan Young

  51 shared

• Elise F. Morgan

  Boston University

  50 shared

• Dana T. Graves

  University of Pennsylvania

  50 shared

• R. Toholka

  Boston University

  50 shared

• L. C. Gerstenfeld

  Boston University

  50 shared

• Anna Smerdel‐Ramoya

  Saint Francis University

  49 shared

• MT Linossier

  Inserm

  49 shared

Labs

• Bais Research GroupPI

Education

• Ph.D., Biotechnology, veterinary medicine

  Indian Veterinary Research Institute

  2004

• Other, Biotechnology, veterinary medicine

  Indian Veterinary Research Institute

  2001

• Other, Veterinary Medicine

  Nagpur Veterinary College

  1998