Sid Puram, MD, PhD

Assistant Professor
Otolaryngology
Division Chief of Head and Neck Surgical Oncology
Genetics

Molecular Genetics and Genomics Program
Cancer Biology Program
Computational and Systems Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-9943

  • Couch Research Building, Room 6110, 4515 McKinley Ave, St Louis MO 63110

  • sidpuram@wustl.edu

  • http://oto.wustl.edu/puramlab

  • https://twitter.com/sidpuram?lang=en

  • tumor heterogeneity; single cell; spatial transcriptomics; head and neck cancer; signaling

  • Understanding the role of tumor heterogeneity in cancer biology, including its contributions to cancer development, growth, metastasis, and treatment resistance mechanisms, in order to translate these insights into new diagnostics and novel therapeutics

Research Abstract:

Our lab is dedicated to understanding the importance of tumor heterogeneity in cancer biology, in particular cancers of the head and neck, which represents the 6th leading cause of cancer-related deaths worldwide. I serve as the Division Chief of Head and Neck Oncology at Washington University, where I lead a vibrant group of researchers including 4 MD/PhD or PhD students, two post-docs, and several staff scientists. Our group is highly collaborative with others on campus, allowing us to leverage our complementary research background to move the field forward in exciting new directions.

In particular, we have been leaders in the use of advanced genomic techniques including single cell approaches, spatial transcriptomics, epigenetic studies, and transcription factor mapping techniques (calling cards) to better understand tumor biology. We complement these approaches with more traditional biochemistry and cell biology approaches to define the mechanisms and cellular states that underlie tumor growth, development, metastasis, and treatment resistance. In addition to providing fundamental insights into cancer biology, our goal is to translate these mechanistic insights into new diagnostics and therapeutics across oncology. Briefly, we hope to accomplish this goal through several major active lines of research:

1) Characterizing expression heterogeneity in head and neck cancer - Using cutting edge single cell techniques, which our lab has pioneered, we are investigating diversity present at the level of diverse individual cells, including malignant, stromal, and immune subpopulations. Although we have begun the difficult work of studying heterogeneity in oral cavity tumors, other subsite of HNSCC as well as other pathologies could greatly benefit from these studies.

2) Understanding how diverse viral expression states may specifically drive HPV-related cancers - Although HPV related head and neck cancers are more favorable in their prognosis, 10-40% of patients will experience tumor recurrence. We have utilized single cell techniques as well as epigenetic studies to define diverse HPVon and HPVoff state, which we believe may predict favorable vs adverse outcomes in their patients. Future work will focus on understand what the key epigenetic drivers of these heterogeneous HPV states may be.

3) Clarifying the key regulatory transcription factors and their targets triggering head and neck cancer - Our prior single cell analysis revealed a partial, hybrid epithelial/mesenchymal state (Cell, 2017) which appears to enable tumors to invade and metastasize. We are now rigorously investigating what transcription factors may underlie this process and using advance genomic approaches including calling cards (bulk and single cell) to comprehensively identify the targets of these TFs. We are also interested in TFs with pathology gain-of-function mutations and determining how these may exert an effect on tumor biology.

4) Interrogating the role of tumor-immune interactions through basic and translational studies - Tumor-host interactions are now established as a core component of cancer biology. The recent advent and adoption of immunotherapeutics across a wide range of cancers highlights the importance of this burgeoning field. We are interested in understanding how the tumor-immune interactions may be mediated through specific ligand-receptor events, as well as how the immune system responds to tumor heterogeneity and unique tumor expression states using advanced genomic approaches. We pair these techniques with ongoing clinical trials to provide a further layer of translational research to this area of interest.

5) Investigating epigenetic and epitranscriptomic drivers in head and neck cancer - Epigenetic regulators of cancer are now well described and highly relevant to cancer development. We are interested in understanding how modification of RNA, rather than DNA (known as epitranscriptomics) may direct the invasion and metastasis of cancer. Specifically, we have been studying the role of m5C, m6A, and other nucleotide modifications as key drivers of these processes.

6) Developing in vitro and in vivo models to study head and neck cancer - Despite substantial interest there are few typified and widely accepted models of head and neck cancer. With access to numerous cell lines, we will characterize existing models in new ways using a combination of mutational and expression-based profiling, thereby validating how well these models recapitulate human tumors and their diversity. However, we are interested in developing more sophisticated models of these human cancers through patient-derived xenografts (PDX), patient-derive organoids (PDO), and potentially syngeneic models that may better allow the immune system and its influence in head and neck cancer to be more accurately studied.

Mentorship and Commitment to Diversity Statement:
As a leader in the clinical and research space in head and neck cancer, I am firmly committed to the mentorship and development of diversity candidates. I strive to mentor every individual to be the best version of themselves. I ask equal engagement from my mentees to help achieve these goals.

Selected Publications:

Highlighted publications from >120 peer-reviewed papers:

Gavish A, Tyler M, Simkin D, Kovarsky D, Gonzales Castro LN, Halder D, Chanoch-Myers R, Laffy J, Mints M, Greenwald AR, Wilder A, Tal R, Spitzer A, Hara T, Tirosh A, Suva ML, Puram SV, Tirosh I. “The transcriptional hallmarks of intra-tumor heterogeneity across a thousand tumors,” BioRxiv and Nature (under review). doi: https://doi.org/10.1101/2021.12.19.473368

Puram SV†,*, Mints M*, Ananya A, Qi Z, Reeb A, Gerndt S, Liu P, Barrett TF, Law T, Parikh AS, Mroz EA, Rocco JW, Ding L, Gay HA, Thorstad WL, Adkins DR, Rich JT, Paniello RC, Pipkorn P, Jackson RS, Wang X, Mazul A, Chernock R, Zevallos JP, Tirosh I†. “Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma,” Nature Genetics (in press).

Parikh AS, Wizel A, Davis D, Lefranc-Torres A, Rodarte-Rascon AI, Miller LE, Emerick KS, Varvares MA, Deschler DG, Faquin WC, Aster JC, Lin DT, Bernstein BE, Drier Y*, Puram SV*. “Single cell RNA-sequencing uncovers a paracrine interaction that may drive oncogenic Notch signaling in human adenoid cystic carcinoma,” Cell Reports (in press).

Zenga J, Atkinson S, Yen T, Massey B, Stadler M, Bruening J, Peppard W, Reuben M, Hayward M, Mesich B, Buchan B, Ledeboer N, Sanchez JL, Fraser R, Lin CW, Holtz ML, Awan M, Wong SJ, Puram SV, Salzman N. “A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome,” EBioMedicine (2022). PMID: 35671624.

Mullins RDZ, Pal A, Barrett TF, Neal MEH, Puram SV†. “Epithelial-mesenchymal plasticity in tumor immune evasion,” Cancer Research 82(13): 2329-2343 (2022). PMID: 35363853.

Pal A, Barrett TF, Paolini R, Parikh AS, Puram SV†. “Partial EMT in head and neck cancer biology: A spectrum instead of a switch,” Oncogene (2021).

Qi Z, Liu Y, Mullins R, Sample RA, Law T, Mazul A, Jackson RS, Kang SY, Pipkorn P, Parikh AS, Tirosh I, Dougherty J, Puram SV†. “Single-cell deconvolution of head and neck squamous cell carcinoma,” Cancers 13(6): 1230 (2021). PMID: 33799782.

Kinker GS, Greenwald AC, Tal R, Orlova Z, Cuoco MS, McFarland JM, Warren A, Rodman C, Roth JA, Bender SA, Kumar B, Rocco JW, Fernandes PACM, Mader CC, Keren-Shaul H, Plotnikov A, Tsherniak A, Rozenblatt-Rosen O, Kriszhanovsky V, Puram SV, Regev A, Tirosh I. “Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity,” Nature Genetics 52(11): 1208-1218 (2020). PMID: 33128048.

Parikh AS, Shin JH, Faquin WC, Lin DT, Tirosh I, Sunwoo JB, Puram SV†. “Malignant cell-specific CXCL14 promotes tumor lymphocyte infiltration in oral cavity squamous cell carcinoma,” Journal for ImmunoTherapy of Cancer 8(2): e001048 (2020). PMID: 32958684.

Parikh AS*, Puram SV*,†, Tirosh I, Faquin WC, Richmon JD, Emerick KS, Deschler DG, Varvares, MA, Bernstein BE, Lin DT†. Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma predicts lymph node metastasis. Oral Oncology 99: 104458 (2019). PMID: 31704557.

Qi Z, Barret TF, Parikh AS, Tirosh I, Puram SV†. “Single cell sequencing and its applications in head and neck cancer,” Oral Oncology 99: 104441 (2019). PMID: 31689639.

Puram SV*, Parikh AS, Tirosh I*. Single cell RNA-sequencing in head and neck cancer highlight a role for a partial epithelial-to-mesenchymal transition, Molecular and Cellular Oncology (2018). 5(3):e1448244.

Puram SV*, Tirosh I*, Parikh A*, Patel AP, Yizhak K, Gillespie S, Rodman C, Luo CC, Mroz EA, Emerick KS, Deschler DG, Varvares MA, Mylvaganam R, Rozenblatt-Rosen O, Rocco JW, Faquin WC, Lin DT, Regev A, Bernstein BE. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer, Cell 171(7): 1611-1624 (2017).

Puram SV, Rocco JW. Molecular biology of head and neck cancer, Hematology Oncology Clinics of North America 29(6): 971-992 (2015).

Puram SV*, Kim AH*, Park HY, Bonni A. The ubiquitin receptor S5a/Rpn10 links centrosomal proteasomes with dendrite development in the mammalian brain, Cell Reports 4(1): 19-30 (2013).

Puram SV, Yeung CM, Asl-Jahani A, Lin C, Jackson-Grusby L, Bonni A. “STAT3-iNOS signaling drives astrocyte proliferation and transformation,” Journal of Neuroscience 32(23): 7806-7818 (2012). PMID: 22674257.

Puram SV, Riccio A, Koirala S, Ikeuchi Y, Kim AH, Corfas G, Bonni A. “A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the mammalian brain,” Genes and Development 25(24): 2659-2673 (2011). PMID: 22135323.

Puram SV, Kim AH, Ikeuchi Y, Riccio A, Wilson-Grady JT, Gygi SP, Bonni A. “A CaMKIIβ signaling pathway at the centrosome regulates dendrite patterning in the brain,” Nature Neuroscience 14(8): 973-983 (2011). PMID: 21725312.

Puram SV, Bonni A. “Novel functions for the anaphase-promoting complex in neurobiology,” Seminars in Cell and Developmental Biology 22(6): 5865-94 (2011). PMID: 21439392.

Kim AH, Puram SV, Bilimoria PM, Ikeuchi Y, Keogh S, Wong M, Rowitch D, Bonni A. “A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in post-mitotic neurons,” Cell 136(2): 322-336 (2009). PMID: 19167333.

Last Updated: 11/20/2022 10:43:02 PM

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