SHIKHAR UTTAM, Ph.D.

Assistant Professor
Department of Computational and Systems Biology,
UPMC Hillman Cancer Center, Cancer Biology Program,
University of Pittsburgh, Pittsburgh, PA, United States.

 

Cancer is a disease with multi-factorial etiology. Our interest in cancer research lies in overcoming the twin challenges of characterizing and understanding this multi-factorial complexity in pre-cancerous lesions and cancerous tumors using a systems biology and biomedical engineering framework. We are particularly interested in developing discovery-based and hypothesis-driven systems and methods to deconstruct the heterogeneity of tumor microenvironments of solid cancers, and help translate that understanding to the clinic. We have a hybrid wet/dry lab setup, and our work draws from diverse disciplines including cancer biology; bioimaging and image analysis; machine learning and bioinformatics; and physics and mathematics.

Recent News

• We will be presenting some results from on going work in our lab at Biomedical Engineering Society (BMES) 2021 Annual Meeting (Oct 6 - 9, 2021; Orlando, Florida)
  • B. Kochetov, R. Raphael, and S. Uttam, "Unsupervised segmentation of complex tissue using multiplexed imaging-derived a priori knowledge," Abstract 074 - 841, BMES 2021 Annual Meeting.
  • S. Leng, J. Xu, Y. Liu, and S. Uttam, "Demonstration of ability of nanoscale nuclear architecture mapping to study chromatin alteration," Abstract reu-011-3129, BMES 2021 Annual Meeting.
  • D. Pitlor, R. E. Brand, B. Dudley, E. Karlowski, A. Zyhowski, E. J. Metter, R. M. Brand, and S. Uttam, "Coefficient of variation based multiplexed ELISA biomarker selection in HNPCC Syndrome Patients", Abstract reu-007-3147, BMES 2021 Annual Meeting.
• We will be presenting our latest results on nanoscale nuclear architecture mapping capturing chormatin reorganization in epithelial cells undergoing malignant transformation at Photonics West 2021.
• Collaborative work led by Drs. Brand and Moore on developing pre-clinical ex vivo system for testing efficacy and target engagement of therapuetics in inflammatory bowel disease is in press. Tofacitinib based JAK/STAT signaling inhibition was used to test the system.

  R. M. Brand, B. A. Moore, A. Zyhowski, A. Siegel, S. Uttam, E. J. Metter, J. Engstrom, R. E. Brand, N. Biswas, D. C. Whitcomb, D. G. Binion, M. Schwartz, I. McGowan, Tofacitinib inhibits inflammatory cytokines from ulcerative colitis and healthy mucosal explants and is associated with p-STAT1/3 reduction in T-cells, Am. J. Physiol. Gastrointest. Liver Physiol. (2020/2021). [in press]

• A study lead by Drs. Das and Singhi on tumor size difference between preoperative endoscopic ultrasound imaging and postoperative pathology in neoadjuvant-treated pancreatic ductal adenocarcinoma patients as a potential prognostic indicator in subsequent chemotherapeutic management is in press.

  R. Das, K. McGrath, N. Seiser, K. Smith, S. Uttam, R. E. Brand, K. E. Fasanella, A. Khalid, J. S. Chennat, S. Sarkaria, H. Singh, A. Slivka, H. J. Zeh, A. H. Zureikat, M. E. Hogg, K. K. Lee, A. Paniccia, M. C. Ongchin, J. F. Pingpank, B. A. Boone, A. K. Dasyam, N. Bahary, V. C. Gorantla, J. C. Rhee, R. Thomas, S. Ellsworth, M. S. Landau, N. Paul Ohori, P. Henn, S. Shyu, B. K. Theisen, A. D. Singhi, Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome, Clin. Gastroenterol. Hepatol. (2020/2021). [in press]

• Shan Leng (Bioengineering) has joined (Dec, 2020) the lab as an undergraduate researcher.
• Dr. Bogdan Kochetov has joined (Dec, 2020) the lab as a Postodoctoral Research Associate.
• Rebecca Raphael has joined (Sep, 2020) the lab as the new lab manager and research technician.
• We presented a poster on our early work on compressed sensing in optical coherence tomography at CLEO 2020. (Dates: May 11 - 15, 2020)

  S. Uttam, Sampling and scrambling in compressive sensing based spectral domain optical coherence tomography, JTu2F.7, CLEO (2020). [link]

• Our paper on risk prognosis of colorectal cancer recurrence in patients that have undergone primary tumor resection and the recurrence-driven spatial systems biology of their tumor microenvironment has been published in Nature Communications. The study utilizes highly multiplexed immunofluorescence imaging.

  S. Uttam, A. M. Stern, S. Furman, F. Pullara, D. Spagnolo, L. Nguyen, A. H Gough, C. Sevinsky, F. Ginty, D. L. Taylor, S. C. Chennubhotla, A spatial analytics computational and systems biology platform predicts risk of colorectal cancer recurrence and identifies emergent spatial domain networks associated with recurrence, Nat. Commun.; 1:3515 (2020). [link]

• Our paper extending nanoscale nuclear architecture mapping (nanoNAM) - derivative of Fourier-domain Optical Coherence Tomography - to three dimensions and its application to detecting colorectal neoplasia in patients with inflammatory bowel disease has been published in Cancer Prevention Research (American Association for Cancer Research (AACR)):

  S. Uttam, J. G. Hashash, J. LaFace, D. Binion, M. Regueiro, D. J. Hartman, R. E. Brand, and Y. Liu,Three-dimensional nanoscale nuclear architecture mapping detects the presence of colorectal neoplasia in patients with inflammatory bowel disease colitis from rectal biopsies, Cancer Prev. Res.,12(8) 527-538 (2019). [link]

It was invited to be featured on the cover of the August 1, 2019 issue of Cancer Prevention Research (AACR).



• R01 CA232593 grant was recently awarded by the National Cancer Institute (NCI) at the National Institutes of Health (NIH). (April 2019 - March 2024)
  
  PIs: Dr. Y. Liu and Dr. S. Uttam
• Invited paper, SPIE/OSA European Conferences on Biomedical Optics (ECBO) 2019:

  S. Uttam and Y. Liu Three-dimensional nanoscale nuclear architecture mapping for improved cancer risk stratification, SPIE/OSA European Conferences on Biomedical Optics (ECBO) 2019, 23-27 June 2019, Munich, Germany; Paper 11076-38 (2019).

• A study on the role of chronic oxidative stress in telomere shortening led by Drs. E. Fouquerel and P. Opresko has been published. I contributed to the data and statistical analysis performed in the study.

  E. Fouquerel, R. Barnes, S. Uttam, S. Watkins, M. Bruchez, and P. L. Opresko, Chronic oxidative guanine base damage at telomeres induces telomere crisis, Molecular Cell; 75(1): 117-130 (2019).

• We have been accepted for a poster presentation at AACR Annual Meeting 2019 in Atlanta, Georgia:

  S. Uttam, A.M. Stern, S. A. Furman, F. Pullara, F. Ginty, D. L. Taylor, S. C. Chennubhotla, Spatial proteomics with hyperplexed fluorescence imaging predicts risk of colorectal cancer recurrence and infers recurrence-specific protein-protein networks. Cancer Res; 79 (13 Supplement): 1642 (2019). [AACR Annual Meeting 2019, March 29-April 3 2019, Atlanta, Georgia].

• Patents 10,156,479 and 9,983,399 were issued in 2018. I am a co-inventor.
• Collaborative work using super-resolution imaging to study chromatin structure of different epigenetic states has been published. My contribution is here.

  J. Xu, H. Ma, J. Jin, S. Uttam, R. Fu, Y. Huang, and Y. Liu, “Super-resolution imaging of higher-order chromatin structures at different epigenetic states in single mammalian cells,” Cell Reports; 24(4): 873-882 (2018).

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