Jacob Gardinier Scott, MD, DPhil
Physician-Scientist
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Location: NE6-306
Phone: (216) 444-5606
Scott Laboratory
Cancer is a complex disease that is an aberration of our own tissues, but it still obeys fundamental biological rules. Our greatest challenge in the clinic is the emergence of resistance to our therapies, a process which is governed by Darwinian evolution. Using a suite of mathematical and experimental models, my laboratory seeks to deconvolute the complexity of the evolutionary process into fundamental principles. We aim to use this knowledge to then curtail the evolutionary process to increase the efficacy of targeted therapies and radiation. This same knowledge can be further harnessed to understand the differences in disease progression and therapy response on a personalized basis, so that the right treatment can be given to the right patient at the right time.
Lay Summary
Our mission is to understand how cancers acquire resistance to targeted biological agents and radiation, and how pathogens evolve antibiotic resistance, and to harness this knowledge to design better therapeutic strategies for our patients.
1. Scott JG. Lee H, Barsoum WK, van den Bogert AJ. “The Effect of Tibiofemoral Loading on Proximal Tibiofibular Joint Motion.”Journal of Anatomy,November 2007;211(5):647-653
PMID: 17764523
2. Elias H , Scott JG, Metheny L, Quereshy F. “Multiple Myeloma Presenting as Mandibular Ill-defined Radiolucent Lesion with Numb Chin Syndrome: a case report.” Journal of Oral and Maxillofacial Surgery, September 2009;67(9):1991-1996
PMID: 19686938
3. Elias H , Scott JG, Metheny L, Quereshy F. “Multiple Myeloma Presenting as Mandibular Ill-defined Radiolucent Lesion with Numb Chin Syndrome: a case report.” Journal of Oral and Maxillofacial Surgery, September 2009;67(9):1991-1996
PMID: 19686938
4. OhS, Scott JG, Suh T, Kim S. “Measurement of Dose Discrepancies Due to Inhomogeneities and Radiographic Contrast in Balloon Catheter Brachytherapy.” Medical Physics, September 2009;36(9):3945-3954
PMID: 19810467
5. Packer CD, Carnell RC, Tomcho PM, Scott JG. “Development of a Four-Day Service-Learning Rotation for Third-Year Medical Students.” Teaching and Learning in Medicine, July 2010;22(3):224-228
PMID: 20563946
6. Scott JG, Tsai Y, Chinnaiyan P, Yu HM. “Effectiveness of Radiotherapy for Elderly Patients with Glioblastoma.” Int J Radiat Oncol Biol Phys. 2011 Sept 1;81(1):206-210
PMID: 20675068 *Highlighted as “Issue Highlight Article” September 2011
7. Basanta D✝, Scott JG✝, Rockne R, Swanson KR, Anderson ARA. “The role of IDH1 mutated tumour cells in secondary glioblastoma: an evolutionary game theoretical view.” Physical Biology. 2011 Feb; 8(1):015016.
PMID: 21301070 *Top 3% of downloaded articles across IOP Journals for 2011
8. Scott JG, Suh JH, Elson P, Barnett GH, Vogelbaum MA, Peereboom DM, Stevens GH, Elinzano H, Chao ST. “Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years or older: a retrospective review of 206 cases.” Neuro Oncology. 2011 Apr;13(4):428-3.
PMID: 21363881 *Highlighted by Editorial - PMID: 21430110
9. Basanta D, Scott JG, Fishman MN, Ayala GE, Hayward SW, Anderson ARA. “Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game.” British Journal of Cancer, 3 Jan 2012; 106(1)1:174-181
PMID: 22134510
10. Finkelstein SE, Rodriguez F, Dunn M, Scott JG, et al. “Knowing when to say when: prospective serial assessment of apoptosis, cell death, and lymphocyte infiltrates during the first clinical experience with intraprostatic autologous dendritic cell injection coordinated with radiation therapy.” Immunotherapy, 2012 Apr; 4(4):373-82
PMID: 22512631
11. Scott JG, Kuhn P, Anderson ARA. “Unifying Metastasis--Integrating intravasation, circulation and end organ colonization.” Nature Reviews Cancer 12, 445-446, Jul 2012
PMID: 22912952*Highlighted by Editorial - PMID: 23303865
12. Scott JG, Bauchet L, Fraum TJ, Nayak L, Cooper AR, Reiner AS, Chao ST, Suh JH, Vogelbaum MA, Peereboom DM, Zouaoui A, Mathieu-Daudé H, Fabbro-Peray P, Rigau V, Taillandier L, Abrey LE, DeAngelis LM, Shih JH, Iwamoto FM. “Recursive Partitioning Analysis Identifies Prognostic Groups for Glioblastoma Patients Aged 70 Years or Older.” Cancer, 15 Nov 2012;118(22): 5595-5600
PMID: 22517216
13. Scott JG, Basanta D, Anderson ARA, Gerlee P. “A mathematical model of tumor self-seeding reveals secondary metastatic deposits as drivers of primary tumor growth.” Journal of the Royal Society: Interface2013, Feb 20;10(82) DOI: 10.1098/rsif.2013.0011
PMID: 23427099
14. McTyre E✝, Scott JG✝, Chainnaiyan P. “Whole Brain Radiotherapy for Brain Metastases.” Surgical Neurology International. 2013 May 2;4(Supp 4):S236-44.
DOI:10.4103/2152-7806.111301 http://goo.gl/4qugt
PMID: 23717795
15. Belmonte-Beitia J, Woolley TE, Scott JG, Maini PK, Gaffney EA. “Modeling biological invasions: Individual to population scaling at interfaces.” Journal of Theoretical Biology 2013, Oct 7;334:1–12 DOI:10.1016/j.jtbi.2013.05.033
PMID: 23770401
16. Scott JG, Chinnaiyan P, Anderson ARA, Hjelmeland A, Basanta D. “Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity.” PLoS Computational Biology 2014, January 16 DOI: 10.1371/journal.pcbi.1003433
PMID: 24453958
17. Baldock AL†, Yagle K†, Born DE, Ahn S, Trister AD, Neal M, Johnston SK,
Bridge C, Basanta D, Scott JG, Malone H, Sonabend AM, Canoll P, Mrugala MM, Rockhill JK, Rockne RC, and Swanson KR. “Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status.” Neuro Oncology 2014, Jun;16(6):779-786DOI: 10.1093/neuonc.nou027 *Highlighted by Editorial
PMID: 24832620
18. Gallaher J, Cook LM, Gupta S, Araujo A, Dhillon J, Park JY, Scott JG, Pow-Sang J, Basanta D, Lynch CC. “Improving treatment strategies for patients with metastatic castrate resistant prostate cancer through personalized computational modeling.” Clinical and Experimental Metastasis. 2014 Dec;31(8):991-9. DOI: 10.1007/s10585-014-9674-1
PMID: 25173680
19. Scott JG, Fletcher AG, Maini PK, Anderson ARA, Gerlee P. “A filter-flow perspective of hematogenous metastasis offers a non-genetic paradigm for personalized cancer therapy” European Journal of Cancer. 2014 Nov;50(17):3068-75DOI:10.1016/j.ejca.2014.08.019
PMID: 25306188
20. Arora D, Frakes J, Scott JG, Opp D, Johnson C, Song J, Harris E. “Incidental radiation to uninvolved internal mammary lymph nodes in breast cancer.” Breast Cancer Research and Treatment. 2015 Jun;151(2):365-72 DOI:10.1007/s10549-015-3400-9
PMID: 25929764
21. Kaznatcheev A✝, Scott JG✝, Basanta D. “Edge effects in game theoretic dynamics of spatially structured tumours.” Journal of the Royal Society: Interface. 2015, 12:20150154. DOI:10.1098/rsif.2015.0154
PMID: 26040596
22. Nichol D, Jeavons P, Bonomo RA, Maini PK, Paul JL, Gatenby RA, Anderson ARA, Scott JG. “Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance.” PLoS Computational Biology 2015 Sep 11: 11(9): e1004493.
DOI:10.1371/journal.pcbi.1004493
PMID: 26360300
23. Scott JG, Fletcher AG, Anderson ARA, Maini PK. “Spatial metrics of tumour vascular organisation predict radiation efficacy in a computational model.” PLoS Computational Biology 2016, Jan 22: 12(1):e1004712
DOI: http://dx.doi.org/10.1101/029595
PMID: 26800503
24. Werner B, Scott JG, Sottoriva A, Anderson AR, Traulsen A, Altrock PM “The Cancer Stem Cell Fraction in Hierarchically Organized Tumors Can Be Estimated Using Mathematical Modeling and Patient-Specific Treatment Trajectories.” Cancer Research. 2016 Apr 1;76(7):1705-13
DOI: 10.1158/0008-5472.CAN-15-2069
PMID: 26833122
25. Naghavi AO, Gonzalez RJ, Scott JG, Mullinax JE, Abuodeh YA, Kim Y, Binitie O, Ahmed KA, Bui MM, Saini AS, Zager JS, Biagioli MC, Letson D, Harrison LB, Fernandez DC “Implications of staged reconstruction and adjuvant brachytherapy in the treatment of recurrent soft tissue sarcoma” Brachytherapy 2016 Jul: 15(4) 495-503
PMID: 27180128
26. Rietman EA, Scott JG, Tuszynski JA, Lakka-Klement G. “Personalized Anticancer Therapy Selection using Molecular Landscape Topology and Thermodynamics” Oncotarget 2016 Oct 26
DOI: http://dx.doi.org/10.18632/concotarget.12932
PMID: 27793055
27. Perni S, Mohamed AS, Scott JG, Enderling H, Garden AS, Gunn GB, Rosenthal DI, Fuller CD. CT-based volumetric tumor growth velocity: A novel imaging prognostic indicator in oropharyngeal cancer patients receiving radiotherapy. Oral Oncology 2016 Dec 31;63:16-22.
DOI: http://dx.doi.org/10.1016/j.oraloncology.2016.10.022
PMID: 27938995
28. Grassberger C, Scott JG, and Paganetti H. "Biomathematical Optimization of Radiation Therapy in the Era of Targeted Agents." International Journal of Radiation Oncology Biology Physics 2017: 13-17.
DOI: http://dx.doi.org/10.1016/j.ijrobp.2016.09.008
PMID: 27979444
29. Scott JG, Berglund A, Schell M, Mihaylov I, Fulp WJ, Yue B, Welsh E, Caudell JJ, Ahmed K, Strom TS, Mellon E, Venkat P, Johnstone P, Foekens J, Lee J, Moros E, Dalton WS, Eschrich SA, McLeod H, Harrison LB, Torres-Roca JF. “A genomic framework for precision radiation therapy” Lancet Oncology 2017 Dec;18:2(202-211)
DOI: http://dx.doi.org/10.1016/S1470-2045(16)30648-9
PMID: 27993569 *Highlighted by Editorial PMID: 27993570
30. Scott JG, Marusyk A. “Somatic clonal evolution: A selection-centric perspective” Biochimica Biophysica Acta - Reviews on Cancer- 2017 Apr 30;1867(2):139-50.
PMID: 28161395
31. Kaznatcheev A, Vander Velde R, Scott JG, Basanta D. “Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature” British Journal of Cancer2017 March 14;116(6):785-792
doi: http://dx.doi.org/10.1101/067488
PMID: 28183139
32. Naghavi AO, Gonzalez RJ, Scott JG, Kim Y, Abuodeh YA, Strom TJ, Echevarria M, Mullinax JE, Ahmed KA, Harrison LB, Fernandez DC “Staged reconstruction brachytherapy has lower overall cost in recurrent soft-tissue sarcoma” Journal of Contemporary Brachytherapy 2017 Feb;9(1):20-29
doi: 10.5114/jcb.2017.65641
33. Naghavi AO, Fernandez DC, Mesko N, Juloori A, Martinez A, Scott JG, Shah C, Harrison LB. American Brachytherapy Society consensus statement for soft tissue sarcoma brachytherapy. Brachytherapy. 2017 Jun 30;16(3):466-89.
doi: https://doi.org/10.1016/j.brachy.2017.02.004
34. Dhawan A, Nichol D, Kinose F, Abazeed M, Marusyk A, Haura E, Scott JG. “Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer” Scientific Reports2017 Apr 27;(1):1232
doi: http://dx.doi.org/10.1038/s41598-017-00791-8
PMID: 28450729
35. McFarland CD, Yaglom JA, Wojtkowiak JW, Scott JG, Morse DL, Sherman MY, Mirny LA. “Passenger DNA alterations reduce cancer fitness in cell culture and mouse models.” Cancer Research 2017 May 23.
36. Ottino-Loffler B, Scott JG, Strogatz SH. “Takeover times for a simple model of network infection” Physical Review E 2017 July 13;96(012313)
doi: https://doi.org/10.1103/PhysRevE.96.012313
37. Zhou M, Scott JG, Chaudhury B, Hall L, Goldgof D, Yeom KW, Iv M, Ou Y, Kalpathy-Cramer J, Napel S, Gillies R. Radiomics in Brain Tumor: Image Assessment, Quantitative Feature Descriptors, and Machine-Learning Approaches. American Journal of Neuroradiology. 2017 Oct 5.
38. Karthik N, Juloori A, Mesko N, Scott JG, Shah CS. “Factors Associated with Acute and Chronic Wound Complications in Patients with Soft-Tissue Sarcoma with Long-Term Follow-up” - in press, American Journal of Clinical Oncology
39. Ottino-Loffler B, Scott JG, Strogatz SH. “Evolutionary dynamics of incubation periods”
eLife 2017;6:e30212
doi: 10.7554/eLife.30212
40. Yoon N, Vander Velde R, Marusyk A, Scott JG. “Optimal therapy scheduling based on a pair of collaterally sensitive drugs.” -in press, Bulletin of Mathematical Biology
preprint: https://www.biorxiv.org/content/early/2017/10/02/196824
41. Kaznatcheev A, Peacock J, Basanta D, Marusyk A, Scott JG. "Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays” - in revisions, Nature Ecology and Evolution
pre-print: http://www.biorxiv.org/content/early/2017/08/21/179259
42. Alfonso JCL, Parsai S, Joshi N, Godley A, Koyfman S, Caudell JJ, Fuller CD, Enderling H, Scott JG. “Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity” - in revisions, Medical Physics
pre-print: http://www.biorxiv.org/content/early/2017/09/03/184044
43. Nichol D, Rutter J, Bryant C, Jeavons P, Anderson ARA, Bonomo RA, Scott JG. “Collateral sensitivity is contingent on the repeatability of evolution” - in revisions, Nature Communications
pre-print: http://www.biorxiv.org/content/early/2017/09/07/185892
44. Dhawan A, Barberis A, Cheng W, Domingo E, West C, Maughan T, Scott JG, Harris AL, Buffa FM. “sigQC: A procedural approach for standardising the evolution of gene signatures.” - in revisions, Nature Protocols
preprint: https://www.biorxiv.org/content/early/2017/10/16/203729
45. Ahmed KA, Scott JG, Arrington JA, Naghavi AO, Grass GD, Perez BA, Caudell JJ, Berglund AE, Welsh EA, Eschrich SA, Dilling TJ, Torres-Roca JF. “Radiosensitivity of Lung Metastases by Primary Histology and Implications for Stereotactic Body Radiotherapy Using the Genomically Adjusted Radiation Dose”. - in press, Journal of Thoracic Oncology.
46. Scott JG, Dhawan A, Hjelmeland A, Lathia J, Chumakova A, Hitomi M, Fletcher AG, Maini PK, Anderson ARA. “Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces.”
preprint: https://www.biorxiv.org/content/early/2017/08/14/169615
47. Dhawan A, Harris A, Buffa FM, Scott JG. “Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network.”
preprint: https://www.biorxiv.org/content/early/2018/03/31/292029
LRI Postdoc Selected for Esteemed Howard Hughes Medical Institute Fellowship
Kyle Card, PhD, a postdoctoral fellow in the Department of Translational Hematology & Oncology Research, has been named a Hanna Gray Fellow by the prestigious Howard Hughes Medical Institute (HHMI). The fellowship—which supports early career researchers and celebrates the importance of diversity in biomedical science—will help support Dr. Card’s postdoctoral work and provide start-up funds for his own laboratory, totaling roughly $1.4 million over eight years.
Combining Genomics and Mathematics Helps Personalize Radiation Therapy for Lung Cancer
Clinical trials in lung cancer over the decades have determined an optimal “one size fits all” dosing scheme for patients treated with radiation therapy, but new research now shows this is not as biologically accurate as once believed. A new technology using tumor genomics to personalize radiation dosing demonstrates that the standard of care approach may be suboptimal for up to 75% of lung cancer patients.
Adapting Ideas from Quantum Physics to Calculate Alternative Interventions for Infection and Cancer
Published in Nature Physics, findings from a new study co-led by Cleveland Clinic and Case Western Reserve University teams show for the first time how ideas from quantum physics can help develop novel drug interventions for bacterial infections and cancer.
Understanding the Balance Between Ecological and Evolutionary Contributors to Cancer
Jacob Scott, MD, DPhil, Department of Translational Hematology and Oncology Research, recently received a five-year, $2.8M grant from the National Cancer Institute, part of the National Institutes of Health, to study how ecological and evolutionary mechanisms contribute to lung cancer development and progression, and how the interplay between these mechanisms may provide novel treatment insights.
When Cancer Cells Compete: Measuring Evolutionary 'Games' in Cancer
Despite rapid advances in targeted therapies for cancer, tumors commonly develop resistance to treatment. When resistance emerges, tumor cells continue to grow unchecked, despite all attempts to slow the progression of the cancer. While mutations in cancer cells significantly affect drug sensitivity, it is increasingly recognized that ecological interactions between cells can also play a role.
Why Unrelated Diseases Follow the Same Incubation Pattern: Lessons from Evolutionary Dynamics, Statistics
When graphed, the incubation periods of many diseases, ranging from polio to measles to leukemia, have the same shape; they are skewed to the right. This means that when incubation periods, or time from pathogen exposure to symptomatic illness, and number of new disease cases in a population are plotted on the x- and y-axes, respectively, the peak of the curve falls on the left side of the graph, with a long tail on the right.
