Sidharth V. Puram, MD, PhD, Assistant Professor, Otolaryngology—Head & Neck Surgery
The primary goal of research in the Puram laboratory is to understand the mechanisms that underlie the growth, development, and spread of head and neck cancers and to determine how these mechanisms may be targeted to develop new diagnostics and therapeutics for this devastating disease. Please use the accordians below to learn more about our research and how you can contribute to our success.
The primary goal of research in the Puram laboratory is to understand the mechanisms that underlie the growth, development, and spread of head and neck cancers and to determine how these mechanisms may be targeted to develop new diagnostics and therapeutics for this devastating disease.
Although the completion of major tumor profiling studies, including those completed by the Cancer Genome Atlas, has dramatically advanced our understanding of head and neck cancers, these prior studies are limited by their use of bulk (pooled) genetic material. As a result, the precise cellular sub-populations with aberrant mutations or gene expression changes are missed. Accordingly, it is impossible to know with these approaches whether a gene that may be upregulated (expressed more highly) came from a tumor cell and thus might represent a potential therapeutic target or whether it came from an immune cell that was fighting the cancer. A detailed understanding of these nuances is critical to developing new diagnostic and therapeutic tools. For example, if a drug was developed to target a gene that arose from immune cells, it may actually accelerate a patient’s disease rather than slow it down. In addition, with the bulk approach, a detailed understanding of the different cells that may be present and their contribution to tumor progression (e.g. stem cells, proliferative cells, quiescent cells) remains unclear, leaving many of the most important challenges in cancer biology (metastasis, treatment resistance, recurrence) unsolved.
Dr. Puram has made major contributions to the field of head and neck through studies that have captured the transcriptional and genetic heterogeneity present in these tumors. These studies were advanced through the use of innovative single cell RNA-sequencing techniques, representing one of the first complete atlases of an epithelial tumor in human patients. In addition, Dr. Puram’s work has provided insights into the mechanisms that may drive cancer spread to lymph nodes (nodal metastasis) by identifying gene programs that may mediate these behaviors in head and neck cancer. These analyses, which represent the first single cell analyses of matched primary and lymph node samples, offer an important glimpse into the complex biology of human tumors.
Utilizing Dr. Puram’s background in biochemistry, cell biology, animal model, and genetics, the laboratory will continue to advance the field of head and neck biology. Prior research into the mechanisms governing developmental neurobiology and glioblastoma serve as a rich foundation for this targeted work, which complements Dr. Puram’s clinical interest in head and neck surgical oncology and microvascular free flap reconstruction.
In the future, the Puram laboratory will expand upon single cell analyses into new tumor subsites and types of tumors in the head and neck. Simultaneously, the lab will build on these findings though modeling using cell lines and animals to better understand the subtle molecular underpinnings in head and neck oncology. These initial studies will lend themselves to downstream chemical and biological screens that can then be directly translated to the clinic and improve patient care and outcomes, ultimately laying the foundation for novel diagnostic and therapeutic approaches in head and neck cancer.
Our lab is dedicated to understanding the mechanisms that underlie the growth, development, and spread of head and neck cancers and to determine how these mechanisms may be targeted to develop new diagnostics and therapeutics for this devastating disease. Please see our research vision for a broad overview of our overarching goals. Briefly, we aim to expand the field of head and neck oncology through several major lines of research:
1) Characterize expression and epigenetic heterogeneity in head and neck cancer – Using cutting edge single cell techniques, which our lab has pioneered, we will investigate 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. Future work will extend to deep analyses of epigenetic heterogeneity to complement studies of expression heterogeneity.
2) Develop 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) and potentially syngeneic models that may better allow the immune system and its influence in head and neck cancer to be more accurately studied.
3) Define the pathways that drive head and neck cancer metastasis, treatment resistance, self-renewal, and immunotherapy response – Our prior work has identified a role for a partial epithelial-to-mesenchymal program in head and neck tumors, specifically oral cavity head and neck squamous cell carcinoma. We will use this foundational work as a starting point and by leveraging standard genetic and biochemical techniques, study this pathway in greater detail including its role in tumor invasion and locoregional and distant metastasis. In the future, we will investigate additional pathways in head and neck cancer that may define drug resistance, self-renewal capabilities, and immunotherapy response.
4) Translating findings into new diagnostics and therapeutics – Due in part to Dr. Puram’s clinical interests, we are highly motivated and well positioned to translate findings from our lab into meaningful changes in patient care. Through large scale pathologic studies using ISH and IHC combined with cutting edge technologies such as multiplexed imaging, we can begin to characterize potential biomarkers in head and neck cancer, while simultaneously utilizing traditional tools in drug discovery to identify targets for novel therapeutics. Our ultimate goal is to move our findings into early pre-clinical and clinical trials that will ultimately dramatically influence the way we manage this challenging disease.
Sid Puram, MD, PhD
Ashley Reeb, BS, RVT
Colleen Richmond, BSN, MPH
Robert Crowder, PhD
Zongtai Qi, PhD
Tom Barrett, MD
We are looking for talented graduate student, post-doctoral fellows, staff scientists, and technicians with strong past experience and excellent educational background who want to join our team! Our lab is located in the Couch Research Building, one of the newest research facilities at Washington University with state-of-the-art space and resources. Please contact us if you are interested in the lab. The opportunity to dramatically alter our understanding, diagnosis, and treatment of human cancers all while working in a collegial, cooperative, and supportive environment await!
Available opportunities in the Puram Lab:
Basic and Translational Research Articles and Reviews:
1. 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). Epub.
2. 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). PMID: 29198524
3. Jahani-Asl A, Yin H, Soleimani VD, Takrima H, Luchman AH, Chang NC, Sincennes MC, Puram SV, Ligon KL, Weiss S, Rudnicki MA, Bonni A. “Control of glioblastoma tumorigenesis by feed-forward cytokine signaling,” Nature Neuroscience 19(6): 798-806 (2016). PMID: 27110918.
4. Puram SV, Rocco JW. “Molecular biology of head and neck cancer,” Hematology Oncology Clinics of North America 29(6): 971-992 (2015). PMID: 26568543.
5. Valnegri P*, Puram SV*, Bonni A. “Regulation of dendrite morphogenesis by extrinsic cues,” Trends in Neuroscience 38(7): 439-447 (2015). PMID: 26100142.
6. 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). PMID: 23831032.
7. Puram SV, Kim AH, Bonni A. “Cell-intrinsic drivers of dendrite morphogenesis,” Development 140(23): 4657-4671 (2013). PMID: 24255095.
8. 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.
9. 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.
10. 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.
11. 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.
12. Puram SV, Kim AH, Bonni A. “An old dog learns new tricks: A novel function for Cdc20-APC in dendrite morphogenesis in neurons,” Cell Cycle 9(3): 482-485 (2010). PMID: 20195072.
13. 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.
14. de la Iglesia N, Puram SV, Bonni A. “STAT3 regulation of glioblastoma pathogenesis,” Current Molecular Medicine 9(5): 580-590 (2009). PMID: 19601808.
15. de la Iglesia N, Konopka G, Puram SV, Chan JA, Bachoo RM, You MJ, Levy DE, Depinho RA, Bonni A. “Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway,” Genes and Development 22(4): 449-462 (2008). PMID: 18258752.
16. Choleris E, Little SR, Mong JA, Puram SV, Langer R, Pfaff DW. “Microparticle-based delivery of oxytocin receptor antisense DNA in the medial amygdala blocks social recognition in female mice,” Proceedings of the National Academy of Sciences 104(11): 4670-4675 (2007). PMID: 17360582.
17. Little SR, Lynn DM, Puram SV, Langer R. “Formulation and characterization of Poly-Beta amino ester microspheres,” Journal of Controlled Release 107(3): 449-462 (2005). PMID: 16112767.
18. Little SR, Lynn DM, Ge Q, Anderson DG, Puram SV, Chen J, Eisen HN, Langer R. “Poly-Beta amino ester-containing microparticles enhance the activity of non-viral genetic vaccines,” Proceedings of the National Academy of Sciences (PNAS) 101(26): 9534-9539 (2004). PMID: 15210954.
Clinical Research Articles:
1. Holbrook EH*, Puram SV*, See RB, Tripp AG, Nair DG. “Artificially induced smell through trans-ethmoid electrical stimulation of the olfactory bulb,” International Forum of Allergy and Rhinology (In press).
2. Yu PK, Rathi VK, Sethi RK, Puram SV, Lin DT, Emerick KS, Durand ML, Deschler DG. “Postoperative care in an intermediate-level medical unit after head and neck microvascular free flap reconstruction,” Laryngoscope Investigative Otolaryngology (In press).
3. Abt NB*, Puram SV*, Sinha S, Sethi RK, Goyal N, Tjoa T, Yarlagadda B, Emerick KS, Rocco JW, Varvares MA, Lin DT, Deschler DG. “Transfusion in head and neck pedicled flap patients: Practice patterns and a comparative analysis by flap type,” Laryngoscope (2018). PMID: 30247764.
4. Sethi RK, Panth N, Puram SV, Varvares MA. “Opioid prescription patterns among patients with head and neck cancer,” JAMA Otolaryngology-Head and Neck Surgery 144(4):382-383 (2018). PMID: 29522065.
5. Abt NB, Sethi RK, Puram SV, Varvares MA. “Preoperative laboratory data predicts complications and surgical site infection in composite head and neck surgical resections,” American Journal of Otolaryngology S0196-0709(17): 31024 (2018). PMID: 29398185.
6. Puram SV†, Bhattacharyya N. “Identifying metrics and factors affecting readmission rate following head and neck cancer surgery,” Otolaryngology Head and Neck Surgery 158(5):860-866 (2018). PMID: 29336226.
7. Rathi VK, Gadkaree SK, Kozin ED, Naunheim MR, Sethi RK, Puram SV, Gray ST. “US Food and Drug Administration Clearance of Moderate-Risk Otolaryngologic Devices via the 510(k) Process, 1997-2016,” Otolaryngology Head and Neck Surgery 157(4): 608-617 (2017). PMID: 28786317.
8. Barber SR, Kozin ED, Remenschneider AK, Puram SV, Smith M, Cunnane ME, Herrmann BS, Brown MC, Lee DJ. “Auditory brainstem implant array position varies widely among adult and pediatric patients and is associated with perception,” Ear and Hearing 38(6): e343-e351 (2017). PMID: 28700445.
9. Abt NB, Xie Y, Puram SV, Richmon JD, Varvares MA. “Frailty Index: Intensive care unit complications in head and neck oncologic regional and free flap reconstruction,” Head and Neck 39(8): 1578-1585 (2017). PMID: 28449296.
10. Puram SV, Chow H, Wu CW, Heaton J, Kamani D, Gorti G, Chiang FY, Dionigi G, Barczynski M, Schneider R, Dralle H, Lorenz K, Randolph GW. “Posterior cricoarytenoid muscle electrophysiologic changes measured with a posterior cricoid electrode are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model,” Laryngoscope 126(12): 2744-2751 (2016). PMID: 27113438.
11. Sinha S*, Puram SV*, Sethi RK, Parikh A, Tjoa T, Goyal N, Yarlagadda BB, Varvares MA, Rocco JW, Emerick KS, Lin D, Durand M, Deschler DG. “Perioperative deep vein thrombosis risk stratification: A comparative analysis of free and pedicled flap patients,” Otolaryngology Head and Neck Surgery 156(1): 118-121 (2016). PMID: 276000631.
12. Puram SV*, Barber SR*, Kozin ED, Shah P, Remenschneider AK, Herrmann BS, Duhaime AC, Barker FG, Lee DJ. “Outcomes following pediatric auditory brainstem implant surgery: Early experiences in a North American center,” Otolaryngology Head and Neck Surgery 155(1): 133-138 (2016). PMID: 27095049.
13. Puram SV†, Bhattacharyya N. “Quality indicators for head and neck oncologic surgery: Academic versis nonacademic outcomes,” Otolaryngology Head and Neck Surgery 155(5): 733-739 (2016). PMID: 27329425.
14. Puram SV, Chow H, Wu CW, Heaton J, Kamani D, Gorti G, Chiang FY, Dionigi G, Barczynski M, Schneider R, Dralle H, Lorenz K, Randolph GW. “Vocal cord paralysis predicted by neural monitoring electrophysiologic changes with recurrent laryngeal nerve compressive neuropraxic injury in a canine model,” Head and Neck 38(S1): E1341-E1350 (2016). PMID: 26348472.
15. Puram SV, Herrmann BS, Barker FG, Lee DJ. “Retrosigmoid craniotomy approach for auditory brainstem implantation: The Massachusetts Eye and Ear-Massachusetts General Hospital experience,” Journal of Neurological Surgery Part B: Skull Base 76(6): 440-450 (2015). PMID: 27054058.
16. Noij KS, Remenschneider AK, Kozin ED, Puram S, Herrmann B, Cohen M, Cunnane MB, Lee DJ. “Direct parasagittal magnetic resonance imaging of the internal auditory canal to determine cochlear or auditory brainstem implant candidacy in children,” Laryngoscope 125(10): 2382-5 (2015). PMID: 25778542.
17. Puram SV, Roberts DS, Niesten ME, Dilger AE, Herrmann BS, Lee DJ. “Cochlear implant outcomes in patients with superior canal dehiscence,” Cochlear Implants International 16(4):213-221 (2015). PMID: 24074366.
18. Puram SV*, Kozin ED*, Sethi RK*, Hight AE, Shrime MG, Gray, ST, Cohen MS, Lee DJ. “Influence of trainee participation on operative times for adult and pediatric cochlear implantation,” Cochlear Implants International 16(3): 175-179 (2015). PMID: 25387322.
19. Puram SV*, Kozin ED*, Sethi RK*, Lee DJ, Alkire B, Gray ST, Shrime MG, Cohen MS. “Impact of resident surgeons on procedure length based on common pediatric otolaryngology cases,” Laryngoscope 125(4): 991-997 (2015). PMID: 25251257.
20. Puram SV, Tward AD, Jung D, Dilger AE, Hermann BS, Dumhaime AC, Barker FG, Lee DJ. “Auditory brainstem implantation in infants: Experience with a 16 month old with cochlear and cochlear nerve hypoplasia,” Otology Neurotology 36(4): 618-624 (2015). PMID: 25473959.
21. Kaplan AB, Kozin ED, Puram SV, Owoc M, Shah P, Hight AE, Remenschneider A, Lee DJ. “Auditory brainstem implant candidacy in the United States in Children 0-17 Years Old,” International Journal of Pediatric Otorhinolaryngology 79(3): 310-315 (2015). PMID: 25577282.
22. Puram SV, Yarlagadda BB, Sethi RK, Muralidhar V, Chambers KJ, Emerick KS, Rocco JW, Lin DT, Deschler DG. “Transfusion in head and neck free flap patients: Practice patterns and a comparative analysis by flap type,” Otolaryngology Head and Neck Surgery 152(3): 449-457 (2015). PMID: 25628368.
Biotek Cytation5 provides cutting edge technology for new assays and techniques
The Cytation5 allows for customized protocols to be written for imaging, quantification and analysis. This results in less time spent counting cells at the scope. The Cytation5 also serves as a plate reader that allows measurement of absorbence, luminescence and fluorescence signals. Other assays include high throughput style screening using automated reagent injectors, nucleic acid and protein quantification, cellular invasion and proliferation assay analysis.
Nikon Ti2-E facilitates new directions
The Nikon Eclipse Ti2 microscope is a great tool for taking high quality publication ready images. Similar to the Cytation5, the Nikon Eclipse Ti2 has built in quantification tools for cell counting and measuring fluorescent signal. The Z-stack module creates in focus 3D images perfect for imaging organoids or sphere cultures. The motorized drive, extra large field of view, auto-exposure, and four different filter wavelengths consistently produce great looking images.
Puram Lab is up and running!
After months of hard work, the Puram lab is a fully functioning lab equipped with new state-of-the art equipment. Our lab manager, Ashley, continues to develop basic lab protocols, create stable cell lines, and generate 10X single cell RNA sequencing libraries which will serve as the foundation for the lab’s research. The Puram lab is eager to build a team of motivated and talented students, faculty, and staff.
Washington University School of Medicine
660 S. Euclid Ave.
Campus Box 8115
St. Louis, MO 63110
For direct inquiries about the lab’s research or scientific opportunities:
Sid Puram, MD PhD
Department of Otolaryngology – Head and Neck Surgery
Department of Genetics
Washington University School of Medicine
For all other questions/inquiries:
Ashley Reeb, BS RVT
Research Lab Supervisor
Department of Otolaryngology – Head and Neck Surgery
Washington University School of Medicine
Make a Gift
The primary goal of the Puram laboratory is to understand the mechanisms that drive challenging aspects of head and neck cancers including resistance to treatment, cancer spread, and recurrence. While tremendous effort has laid the ground work for an overarching view of these devastating cancers, significant room remains in understanding how these tumors may function at the level of individual cells. A detailed understanding of what each cell in a tumor is doing can deepen our understanding of the behaviors and processes that result in poor patient outcomes.
Our laboratory harnesses cutting edge technology using advanced sequencing techniques (e.g. single cell sequencing) along with a detailed understanding of biochemistry, cell biology, and animal models to characterize this challenging disease. As the sixth leading cause of cancer, head and neck cancers result in tens of thousands of deaths each year, demanding our energy, time, and resources until this disease is eradicated.
Research in the Puram laboratory is generously supported by private philanthropic foundations and gifts. However, the tech-heavy nature of our research and the desire to use the most up-to-date techniques in fighting this disease requires significant financial resources, and with greater support, our work can reach new heights and possibilities. If you wish to support our research with a gift, please contact Dr. Sid Puram or the the Development Office at Washington University School of Medicine to determine how your contributions can advance our cause and improve the lives of patients with head and neck cancer.