Biography
Dr. Singh received B.Tech in Biotechnology in 2011 from Indian Institute of Technology Roorkee (IIT Roorkee). He earned his Doctor of Philosophy (Ph.D. in Cell and Systems Biology) degree from University of Toronto in 2021. Following his PhD degree he completed Post-Doctoral Fellowship at the BC Cancer, part of the Provincial Health Services (PHSA) in Vancouver.
Personal Statement
As Assistant Professor at UNM School of Medicine, Dr. Gurdeep Singh spearheads cutting-edge research that decodes intricate epigenetic mechanisms and functional genomics determinants driving pathogenesis of eye diseases and cancer. Leveraging these breakthrough discoveries, his mission is to advance personalized therapeutics, diagnostics, and clinically relevant transformative translational strategies aimed at curing eye diseases/blindness and cancer. Dr. Gurdeep Singh is also Full Member at UNM Comprehensive Cancer Center under Cellular & Molecular Oncology research program. Overall, in his prior research before starting his lab at UNM, Dr. Singh employed powerful tools in molecular biology, single-cell biology, bioinformatics, next-generation sequencing, machine learning, and computational biology to decode the genome sequences and epigenetic signatures driving cellular function, gene regulation and pathogenesis.
His research at Mass. Eye and Ear/Harvard Medical School delved deep into the intricate pathogenesis of ocular diseases and viral evolution. During his PhD at the University of Toronto, he identified the genome sequence code that confers enhancer activity in embryonic stem cells and other tissues using functional genomics experiments and computational approaches, revolutionizing our understanding of gene regulation. Additionally, his novel investigation into the epigenomic alterations instigated by macroH2A.1 (histone variant) in the hippocampus of mice pinpointed its pivotal role in driving gene expression changes during fear conditioning. Subsequently, for his Post-doctoral research at BC Cancer, he focused on decoding the epigenetic/epigenomic regulation (DNA methylation and histone modification) responsible for cancer pathogenesis associated with different mutational backgrounds in breast and ovarian cancer using single-cell experimental approaches. His endeavors also encompassed decoding the mechanisms underlying cancer drug resistance and metastasis, driving the necessary transcriptional reprogramming.
Singh EpiCure Lab: Epigenetics in Cancers & Diseases
Current projects:
A) Projects in Dr. Singh lab are aimed at reducing the metastatic cancer deaths by pinpointing key common epigenetic drivers and rewired enhancers in Uveal Melanoma (UM) i.e. ocular tumor and other cancers with high metastatic instances e.g. high grade serous ovarian cancer (HGSOC). Also, Dr. Singh lab aims to validate new epigenetic therapeutic strategies using Zebrafish UM model and develop methods for early detection of metastasis using cell-free DNA.
B) Dr. Singh lab aims to decode the epigenomic/enhancer rewiring that drives Age-related macular degeneration (AMD) (that leads to vision loss) using human retinal organoid models by exploring the role of AMD-specific single-nucleotide polymorphisms (SNPs), inflammation drivers, epigenetic clock, histone variants and transcriptional reprogramming. As there are no therapeutics available for AMD, hence Dr. Singh lab using computational modeling of AMD epigenetic mechanisms and organoid models will develop drugs and potential therapies for AMD clinical application.
Areas of Specialty
Functional genomics; Epigenetics/Epigenomics; Cancer & Stem Cell Biology; Molecular Biology; Computational Biology.
Achievements & Awards
BC Cancer 2023-2024 Rising Stars Post-Doctoral Fellowship Award
Best Poster Prize, Clinical Epigenetics International Conference 2023
Ontario Graduate Scholarship - International, Government of Ontario (2019-20)
Connaught International Scholarship for Doctoral Students (2014-19)
Elizabeth Ann Wintercorbyn Award, University of Toronto (2019)
Zoology International Scholarship, University of Toronto (2017)
Arts & Science International Graduate Scholarship, University of Toronto (2015)
Key Publications
Journal Article
Singh, Gurdeep, Mullany, Shanelle, Moorthy, Sakthi, D Zhang, Richard, Mehdi, Tahmid, Tian, Ruxiao, Duncan, Andrew, G Moses, Alan, M Mitchell, Jennifer, A 2021 A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells. Genome Research https://doi.org/10.1101/gr.272468.120
Journal Article
Zhang, Hai-Feng, Delaidelli, Alberto, Javed, Sumreen, Turgu, Busra, Morrison, Taylor, Hughes, Christopher, S Yang, Xiaqiu, Pachva, Manideep, Lizardo, Michael, Singh, Gurdeep, Hoffmann, Jennifer, Huang, Yue Zhou, Patel, Khushbu, Shraim, Rawan, Kung, Sonia, HY 2023 A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN -amplified neuroblastoma. Science Advances https://doi.org/10.1126/sciadv.adg6693
Journal Article
Singh, Gurdeep, Stefanelli, Gilda, Narkaj, Klotilda, Brimble, Mark, A Creighton, Samantha, D McLean, Timothy, AB Hall, Meaghan, Mitchnick, Krista, A Zakaria, Jacqueline, Phung, Thanh, Reda, Anas, Leonetti, Amanda, M Monks, Ashley, Ianov, Lara, Winters, Boyer, D 2022 Histone macroH2A1 is a stronger regulator of hippocampal transcription and memory than macroH2A2 in mice. Communications Biology https://doi.org/10.1038/s42003-022-03435-4
Journal Article
Kabeer, Farhia, Tran, Hoa, Andronescu, Mirela, Singh, Gurdeep, Lee, Hakwoo, Salehi, Sohrab, Biele, Justina, Brimhall, Jazmine, Gee, David, Cerda, Viviana, Flanagan, Ciara , HO Algara, Teresa, Kono, Takako, Lai, Daniel, Zaikova, Elena, 2024 Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers. Genome Biology, vol. 25, Issue 191 https://doi.org/10.1186/s13059-024-03318-3
Journal Article
Moorthy, Sakthi, D Davidson, Scott, Shchuka, Virlana, Singh, Gurdeep, Malek-Gilani, Nakisa, Langroudi, Lida, Martchenko, Alexandre, So, Vincent, Macpherson, Neil, N Mitchell, Jennifer, A 2016 Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes. Genome Research
Gender
Male
Languages
- English
- Punjabi
Research and Scholarship
Decoding landscapes of histone modifications, DNA Methylation, and transcription factors binding to define transcriptional reprogramming and mechanisms driving Cancer Pathogenesis, Metastasis, and Drug Resistance: In this research area, I focused on the critical role of epigenetic rewiring in cancer pathogenesis, progression, and drug resistance. I led and supervised CUT&RUN experiment methodology in a study published in ‘Science Advances’ that explored the role of the transcription factor GREB1 in MYCN-amplified neuroblastoma, deciphering its involvement in secretome reprogramming and metastasis. In another project, I decoded major epigenetic rewiring paths in high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC). I identified distinct epigenomic landscapes corresponding to different mutational signatures (HRD and FBI). In another publication in ‘Genome Biology’, we decoded transcriptional reprogramming in TNBC at single-cell level induced by cisplatin drug treatment. Moreover, to further explore cancer drug resistance, in another project, I mapped CpG methylation landscape of cisplatin-resistant and sensitive clones in 3 TNBC tumor PDXs lines for 3 different passages under the following cisplatin conditions: ‘drug-naïve’, ‘cisplatin-resistant’, and ‘drug holiday passages’. Therefore, my research provides a foundation for developing therapies targeting tumor-specific epigenetic rewiring to improve treatment efficacy and overcome resistance in cancer patients. Another work from my Post-doc is contrasting copy-number clone metastatic fitness with metastatic transcriptional reprogramming.
Unraveling the Non-Coding Genome through Molecular & Computational Biology, Comparative Epigenomics, and Synthetic Enhancer Modeling: In this project, I advanced the understanding of the non-coding genome’s functional elements. I decoded the code of enhancers in mammalian genomes using a combination of epigenomics, molecular biology, computational biology, and bioinformatics. I developed a new model, the 'TFBS threshold enhancer model,' based on comparative epigenomics to understand enhancer functionality (Singh et al. 2021, Genome Research). My model allows the creation of synthetic enhancers with robust activity equivalent to natural enhancers, surpassing the limitations of previous models relying on pluripotency master regulators binding sequences. My work provides a better understanding of the sequence code of enhancers, offering valuable insights into genome function with implications for disease diagnosis and treatment as personalized genome information becomes increasingly integrated into healthcare practices.
Investigating the Role of Histone Variants macroH2A1 and macroH2A2 in Memory Formation and Gene Expression Regulation: In this project, I decoded the role of histone variants macroH2A1 and macroH2A2 in the mouse hippocampus and their impact on memory formation and regulation of memory-specific genes (Singh et al. 2022, Communications Biology). Using ChIP-seq and RNA-seq, I revealed that macroH2A1 is dynamically regulated during learning, with its removal associated with increased expression of memory-specific genes, such as Arc. My study sheds light on the unique evolved functions of these histone variants, providing insights into the epigenomic landscape modulation in the hippocampus. In summary, my research contributes to unraveling the crucial role of histone variants and understanding of molecular mechanisms and transcriptional regulators that govern this landscape for the advancement of future cancer therapeutics and epigenetic interventions.
Advancing ocular pathogenesis and viral genomics: I published multiple papers on whole genome sequencing and analysis of previously unsequenced HAdV-D serotypes. I investigated epidemic keratoconjunctivitis (EKC) caused by human adenovirus species D (HAdV-D), decoding viral genomes to understand EKC pathogenesis. I found novel recombination within multiple HAdV-Ds, including HAdV-D56, an adenovirus causing neonatal fatality and keratoconjunctivitis. I identified homologous recombination as a major evolutionary mechanism, influencing viral ontogeny through coinfections. My work advances viral genomics by establishing whole genome sequencing as the standard for adenovirus characterization, contributing to a new typing system based on genomics rather than serology.