Mark Robertson-Tessi, PhD

My research focuses on the integration of mathematical modeling with both experimental and clinical data to deepen our understanding of the dynamic mechanisms at work in cancer. A primary goal of these efforts is to develop decision support tools that leverage longitudinal data to guide personalized therapy.

Associations

• Integrated Mathematical Oncology

1) Dynamic clinical decision support frameworks for implementing evolutionary therapies. Many challenges exist to implementing a real-time decision support framework based on large data sets and mathematical modeling. I have been tackling aspects of this problem since my first year at Moffitt, when I helped develop a decision support tool for undetectable breast cancer metastases in the inaugural IMO workshop. More recently, the opportunity to implement these ideas in the clinic became reality with the clinical trial for the Evolutionary Tumor Board (ETB), where mathematical modeling and data analysis are used to generate predictions of patient response to available treatment options. My role in the ETB, which has been enrolling patients since 2020, was to develop and implement novel techniques for using both individual and cohort patient data to predict treatment response and identify alternative optimal strategies for patients. To date, we have enrolled 21 patients in the trial and have developed many novel methods that will serve as the foundation for upcoming evolutionary therapy trials. We are in the process of submitting the first two papers on the ETB, and the approach is extending into a number of new trials in this space, including a multi-institution ETB for pediatric cancers (MCC 22170) of which I am co-PI with Jonathan Metts. 2) Tumor-immune interactions and immunotherapies. Starting with my Ph.D. research and continuing at Moffitt, I have studied the dynamics of immune cells and associated signaling molecules in response to a growing tumor. The complex and dual-edged nature of the immune response, with its pro- and anti-tumor elements, leads to a rich landscape of interactions that benefits from mathematical modeling approaches. Across several diverse tumor-immune models, the repeated observation of personalized “Goldilocks windows” of immunotherapy suggests that there is room to improve the delivery of such treatments in the clinic. 3) Phenotypic heterogeneity, natural selection, and the tumor microenvironment. My major project upon starting as a postdoc was developing a detailed and calibrated mechanistic model of vascular tumor growth, in the context of aerobic glycolysis and acid-mediated invasion. The model included evolving cellular metabolism and a dynamic microenvironment. This work drew upon the interdisciplinary knowledge and data being generated by Moffitt’s Physical Sciences in Oncology U54 center grant. The model predicted many interesting and unintuitive phenomena that were subsequently validated in parallel experimental systems. Several additional studies extended and adapted this model, leading the conceptualization and development of a model-building platform (Hybrid Automata Library, aka HAL) that is now being used in the wider mathematical oncology field. In addition, the model was the basis of the ‘Cancer Crusade’ mobile game, an NIH funded citizen-science initiative that led to a subsequent collaboration with Lawrence Livermore National Laboratory, where we used machine learning approaches to identify optimal treatment policies for patient cohorts.

• West J, Rentzeperis F, Adam C, Bravo R, Luddy KA, Robertson-Tessi M, Anderson ARA. Tumor-immune metaphenotypes orchestrate an evolutionary bottleneck that promotes metabolic transformation. Front Immunol. 2024 Feb.15:1323319. Pubmedid: 38426105. Pmcid: PMC10902449.
• Strobl MAR, Gallaher J, Robertson-Tessi M, West J, Anderson ARA. Treatment of evolving cancers will require dynamic decision support. Ann Oncol. 2023 Oct.34(10):867-884. Pubmedid: 37777307.
• Welch DL, Fridley BL, Cen L, Teer JK, Yoder SJ, Pettersson F, Xu L, Cheng CH, Zhang Y, Alexandrow MG, Xiang S, Robertson-Tessi M, Brown JS, Metts J, Brohl AS, Reed DR. Modeling phenotypic heterogeneity towards evolutionarily inspired osteosarcoma therapy. Sci Rep. 2023 Nov.13(1):20125. Pubmedid: 37978271. Pmcid: PMC10656496.
• West J, Adler F, Gallaher J, Strobl M, Brady-Nicholls R, Brown J, Robertson-Tessi M, Kim E, Noble R, Viossat Y, Basanta D, Anderson ARA. A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation. Elife. 2023 Mar.12. Pubmedid: 36952376. Pmcid: PMC10036119.
• Strobl M, Martin AL, West J, Gallaher J, Robertson-Tessi M, Gatenby R, Wenham R, Maini P, Damaghi M, Anderson A. Adaptive therapy for ovarian cancer: An integrated approach to PARP inhibitor scheduling. bioRxiv. 2023 Mar. Pubmedid: 36993591. Pmcid: PMC10055330.
• Gatenbee CD, Baker AM, Prabhakaran S, Swinyard O, Slebos RJC, Mandal G, Mulholland E, Andor N, Marusyk A, Leedham S, Conejo-Garcia JR, Chung CH, Robertson-Tessi M, Graham TA, Anderson ARA. Virtual alignment of pathology image series for multi-gigapixel whole slide images. Nat Commun. 2023 Jul.14(1):4502. Pubmedid: 37495577. Pmcid: PMC10372014.
• Gallaher J, Strobl M, West J, Gatenby R, Zhang J, Robertson-Tessi M, Anderson ARA. Intermetastatic and Intrametastatic Heterogeneity Shapes Adaptive Therapy Cycling Dynamics. Cancer Res. 2023 Aug.83(16):2775-2789. Pubmedid: 37205789. Pmcid: PMC10425736.
• West J, Robertson-Tessi M, Anderson ARA. Agent-based methods facilitate integrative science in cancer. Trends Cell Biol. 2023 Apr.33(4):300-311. Pubmedid: 36404257.
• Gabbutt C, Schenck RO, Weisenberger DJ, Kimberley C, Berner A, Househam J, Lakatos E, Robertson-Tessi M, Martin I, Patel R, Clark SK, Latchford A, Barnes CP, Leedham SJ, Anderson ARA, Graham TA, Shibata D. Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues. Nat Biotechnol. 2022 May.40(5):720-730. Pubmedid: 34980912. Pmcid: PMC9110299.
• Prabhakaran S, Gatenbee C, Robertson-Tessi M, West J, Beg AA, Gray J, Antonia S, Gatenby RA, Anderson ARA. Mistic: An open-source multiplexed image t-SNE viewer. Patterns (N Y). 2022 Jul.3(7):100523. Pubmedid: 35845830. Pmcid: PMC9278502.
• Strobl MAR, Gallaher J, West J, Robertson-Tessi M, Maini PK, Anderson ARA. Spatial structure impacts adaptive therapy by shaping intra-tumoral competition. Commun Med (Lond). 2022 Apr.2:46. Pubmedid: 35603284. Pmcid: PMC9053239.
• Gatenbee CD, Baker AM, Schenck RO, Strobl M, West J, Neves MP, Hasan SY, Lakatos E, Martinez P, Cross WCH, Jansen M, Rodriguez-Justo M, Whelan CJ, Sottoriva A, Leedham S, Robertson-Tessi M, Graham TA, Anderson ARA. Immunosuppressive niche engineering at the onset of human colorectal cancer. Nat Commun. 2022 Apr.13(1):1798. Pubmedid: 35379804. Pmcid: PMC8979971.
• Foo J, Basanta D, Rockne RC, Strelez C, Shah C, Ghaffarian K, Mumenthaler SM, Mitchell K, Lathia JD, Frankhouser D, Branciamore S, Kuo YH, Marcucci G, Vander Velde R, Marusyk A, Hang S, Hari K, Jolly MK, Hatzikirou H, Poels K, Spilker M, Shtylla B, Robertson-Tessi M, Anderson ARA. Roadmap on plasticity and epigenetics in cancer. Phys Biol. 2022 Apr.19(3). Pubmedid: 35078159. Pmcid: PMC9190291.
• Damaghi M, West J, Robertson-Tessi M, Xu L, Ferrall-Fairbanks MC, Stewart PA, Persi E, Fridley BL, Altrock PM, Gatenby RA, Sims PA, Anderson ARA, Gillies RJ. The harsh microenvironment in early breast cancer selects for a Warburg phenotype. Proc Natl Acad Sci U S A. 2021 Jan.118(3). Pubmedid: 33452133. Pmcid: PMC7826394.
• Strobl MAR, West J, Viossat Y, Damaghi M, Robertson-Tessi M, Brown JS, Gatenby RA, Maini PK, Anderson ARA. Turnover Modulates the Need for a Cost of Resistance in Adaptive Therapy. Cancer Res. 2021 Feb.81(4):1135-1147. Pubmedid: 33172930. Pmcid: PMC8455086.
• Cassidy T, Nichol D, Robertson-Tessi M, Craig M, Anderson ARA. The role of memory in non-genetic inheritance and its impact on cancer treatment resistance. PLoS Comput Biol. 2021 Aug.17(8):e1009348. Pubmedid: 34460809. Pmcid: PMC8432806.
• West J, Schenck RO, Gatenbee C, Robertson-Tessi M, Anderson ARA. Normal tissue architecture determines the evolutionary course of cancer. Nat Commun. 2021 Apr.12(1):2060. Pubmedid: 33824323. Pmcid: PMC8024392.
• Lakatos E, Williams MJ, Schenck RO, Cross WCH, Househam J, Zapata L, Werner B, Gatenbee C, Robertson-Tessi M, Barnes CP, Anderson ARA, Sottoriva A, Graham TA. Evolutionary dynamics of neoantigens in growing tumors. Nat Genetics. 2020 Oct.52(10):1057-1066. Pubmedid: 32929288. Pmcid: PMC7610467.
• Bravo RR, Baratchart E, West J, Schenck RO, Miller AK, Gallaher J, Gatenbee CD, Basanta D, Robertson-Tessi M, Anderson ARA. Hybrid Automata Library: A flexible platform for hybrid modeling with real-time visualization. PLoS Comput Biol. 2020 Mar.16(3):e1007635. Pubmedid: 32155140. Pmcid: PMC7105119.
• El-Kenawi A, Gatenbee C, Robertson-Tessi M, Bravo R, Dhillon J, Balagurunathan Y, Berglund A, Vishvakarma N, Ibrahim-Hashim A, Choi J, Luddy K, Gatenby R, Pilon-Thomas S, Anderson A, Ruffell B, Gillies R. Correction: Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Brit J Cancer. 2020 Mar.122(7):1118. Pubmedid: 31937927. Pmcid: PMC7109119.
• Park DS, Luddy KA, Robertson-Tessi M, O'Farrelly C, Gatenby RA, Anderson ARA. Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies. Cancer Res. 2020 Dec.80(23):5147-5154. Pubmedid: 32934022.
• Park DS, Robertson-Tessi M, Luddy KA, Maini PK, Bonsall MB, Gatenby RA, Anderson ARA. The Goldilocks Window of Personalized Chemotherapy: Getting the Immune Response Just Right. Cancer Res. 2019 Oct.79(20):5302-5315. Pubmedid: 31387920. Pmcid: PMC6801094.
• El-Kenawi A, Gatenbee C, Robertson-Tessi M, Bravo R, Dhillon J, Balagurunathan Y, Berglund A, Visvakarma N, Ibrahim-Hashim A, Choi J, Luddy K, Gatenby R, Pilon-Thomas S, Anderson A, Ruffell B, Gillies R. Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Brit J Cancer. 2019 Oct.121(7):556-566. Pubmedid: 31417189. Pmcid: PMC6889319.
• Nichol D, Robertson-Tessi M, Anderson ARA, Jeavons P. Model genotype-phenotype mappings and the algorithmic structure of evolution. J R Soc Interface. 2019 Nov.16(160):20190332. Pubmedid: 31690233. Pmcid: PMC6893500.
• Robertson-Tessi M, El-Kareh A, Goriely A. Corrigendum to ``A mathematical model of tumor-immune interactions'' [Journal of Theoretical Biology 294 (2012) 56-73]. J Theor Biol. 2019 Mar.464:180. Pubmedid: 30610834.
• Robertson-Tessi M, El-Kareh A, Goriely A. Corrigendum to ``A model for effects of adaptive immunity on tumor response to chemotherapy and chemoimmunotherapy'' [Journal of Theoretical Biology 380 (2015) 569-584]. J Theor Biol. 2019 Mar.464:181. Pubmedid: 30610835.
• West J, Robertson-Tessi M, Luddy K, Park DS, Williamson DFK, Harmon C, Khong HT, Brown J, Anderson ARA. The Immune Checkpoint Kick Start: Optimization of Neoadjuvant Combination Therapy Using Game Theory. JCO Clin Cancer Inform. 2019 Feb.3:1-12. Pubmedid: 30742484. Pmcid: PMC6873943.
• Yagawa Y, Robertson-Tessi M, Zhou SL, Anderson ARA, Mulé JJ, Mailloux AW. Systematic Screening of Chemokines to Identify Candidates to Model and Create Ectopic Lymph Node Structures for Cancer Immunotherapy. Sci Rep. 2017 Nov.7(1):15996. Pubmedid: 29167448. Pmcid: PMC5700067.
• Ibrahim-Hashim A, Robertson-Tessi M, Enrizues-Navas P, Damaghi M, Balagurunathan Y, Wojtkowiak JW, Russell S, Yoonseok K, Lloyd MC, Bui MM, Brown JS, Anderson AR, Gillies RJ, Gatenby RA. Defining Cancer Subpopulations by Adaptive Strategies Rather Than Molecular Properties Provides Novel Insights into Intratumoral Evolution. Cancer Res. 2017 May.77(9):2242-2254. Pubmedid: 28249898. Pmcid: PMC6005351.
• Poleszczuk J, Luddy KA, Prokopiou S, Robertson-Tessi M, Moros EG, Fishman M, Djeu JY, Finkelstein SE, Enderling H. Abscopal Benefits of Localized Radiotherapy Depend on Activated T-cell Trafficking and Distribution between Metastatic Lesions. Cancer Res. 2016 Mar.76(5):1009-1018. Pubmedid: 26833128.
• Nichol D, Robertson-Tessi M, Jeavons P, Anderson AR. Stochasticity in the Genotype-Phenotype Map: Implications for the Robustness and Persistence of Bet-Hedging. Genetics. 2016 Dec.204(4):1523-1539. Pubmedid: 27770034. Pmcid: PMC5161283.
• Robertson-Tessi M, El-Kareh A, Goriely A. A model for effects of adaptive immunity on tumor response to chemotherapy and chemoimmunotherapy. J Theor Biol. 2015 Sep.380:569-584. Pubmedid: 26087282.
• Robertson-Tessi M, Anderson AR. Big Bang and context-driven collapse. Nat Genetics. 2015 Mar.47(3):196-197. Pubmedid: 25711865.
• Robertson-Tessi M, Gillies RJ, Gatenby RA, Anderson AR. Impact of metabolic heterogeneity on tumor growth, invasion, and treatment outcomes. Cancer Res. 2015 Apr.75(8):1567-1579. Pubmedid: 25878146. Pmcid: PMC4421891.
• Luddy KA, Robertson-Tessi M, Tafreshi NK, Soliman H, Morse DL. The role of toll-like receptors in colorectal cancer progression: evidence for epithelial to leucocytic transition. Front Immunol. 2014 Oct.5:429. Pubmedid: 25368611. Pmcid: PMC4202790.
• Robertson-Tessi M, El-Kareh A, Goriely A. A mathematical model of tumor-immune interactions. J Theor Biol. 2012 Feb.294:56-73. Pubmedid: 22051568.

• Title: STEER: Strategy for Therapeutic Extinction of Evolving Resistance in lung cancer
  Sponsor: Moffitt Cancer Center
  PI (Contact): Robertson-Tessi, M., CO-PI: Marusyk, A.
• Title: Feasibility of Generating Novel Translational and Therapeutic Strategies based on a Multicenter, Pediatric and AYA Evolutionary Tumor Board; pedsETB
  Sponsor: Florida Biomedical Research Program (FBRP)
  PI: Metts, J., CO-PI: Robertson-Tessi, M., CO-PI: Anderson, A., CO-PI: Brown, J., CO-PI: Marusyk, A.