Draft:Peter Kuhn

Kuhn grew up on a farm in Bavaria in the small town of Unterpleichfeld of approximately 1,000 residents, where his family ran an orchard of pears, plums and apples.  He is the youngest of five children and lived a charmed childhood until the day his mother found a lump in her breast. Her cancer diagnosis led to experimental cancer treatments. Years later, Kuhn took on the challenge to study how cancer invades the human body.⁴

In 1992, Kuhn earned his bachelor’s degree at Julius Maximilians Universität Würzburg, Germany. He came to the U.S. in 1993 as an exchange student and while attending a lecture in New York that showed the power of targeted drug design, he was inspired to stay and study biomedicine. He completed his postgraduate degrees of Masters in Science and received his PhD in 1995 at Wadsworth Center, New York State Department of Health and Physics Department, State University of New York at Albany, NY.

After obtaining his Ph.D., Kuhn joined Stanford University in the faculties of Medicine and Accelerator Physics as a tenured track Assistant Professor. Here he focused on multi-scale human biology and time dynamics of biological processes. Starting with atomic resolution structural biology and enzyme mechanism timescales, his work was grounded in initial ultra-high resolution studies which required a series of technology innovations that led to scientific discoveries. The science is widely recognized and the methods of systematic synchrotron data collection are now in widespread use in structural biology with close to ten thousand citations across that entire body of work. His involvement was in building and leading the team at Stanford that innovated to solve specific scientific problems as well as founding and co-leading the initial large scale efforts in structural genomics.^5-7

In 1999, he united efforts with Dr. Raymond Stevens on their long mutual interest on G protein–coupled receptors (GPCRs) which constitute the largest integral membrane protein family in the human genome, with almost 1000 members. GPCRs are major contributors to the information flow into cells and, as such, are associated with a multitude of diseases - from diabetes to heart disease, cancer to embryonic development, neurodegenerative diseases like Alzheimer’s and Parkinson’s to our very sense of taste and smell - that make members of this family important pharmacological targets. Kuhn led and co-led structural studies with specific scientific and technological breakthroughs through the structure solution of unique human GPCR structures, the significance of each new receptor demonstrated by the high profile journal where the work was ultimately published including Science and Structure.^8-13

In 2002 Kuhn accepted a position of tenured Associate Professor in the Department of Cell and Molecular Biology at the Scripps Research Institute in La Jolla, CA.  Soon after he began to dedicate a larger part of his time on personalizing medicine and individualized cancer patient care. He went on to establish the Physics Oncology program at the Scripps Research in La Jolla, CA, work published and funded through the National Institutes of Health, National Cancer Institute. It was during this time that Kuhn devised a way to test for cancer cells in the blood through “a liquid biopsy”.^14-17 Epic was founded in 2008 to develop medical diagnostics characterizing circulating tumor cells, and this technology was licensed from Scripps Research Institute based on inventions made by Peter Kuhn's lab at Scripps.^18,19

In the winter of 2014, Kuhn accepted the opportunity to relocate his laboratory to the University of Southern California, Los Angeles, as Dean’s Professor of Biological Sciences to help anchor the USC Michelson Center where he is leading the Convergent Science Institute in Cancer.  His current and ongoing work using the liquid biopsy is focused on the High Definition Single Cell Assay (HD-SCA) workflow that uses the ‘No-Cell-Left-Behind’ approach to identify rare cancer cells and then characterizes these cells by single cell genomics and single cell proteomics. The ultimate goal is to modify outcomes for the diagnosis, prognosis and therapy management of breast, lung, colon, prostate and other tissue cancers.^20-24  https://kuhn.usc.edu/liquid-biopsy/).

Complementary to the single patient studies, Kuhn has undertaken a large scale mathematical model development that has enabled a probabilistic description of cancer progression as a multidirectional process. The creation of mathematical models may guide optimal anatomical sites for local therapy, but these models require clinical validation of their predictive ability. This led him to the current phase of research which now brings together the single cell/single time point characterization of the disease with the evolution of the disease in an integrated model.^25-28

Adding to the areas of focus above, Kuhn is also co-leading a team to focus on digitizing patient performance status. A more objective and precise estimate of patient performance status has the potential to improve toxicity attribution and identify those patients who are most at risk for patient and disease-induced adverse events. Along with Dr. Jorge Nieva, a long-time collaborator, they are evaluating the ability of in-office and at home movement trackers to predict which patients on early phase clinical trials are most likely to experience serious adverse events and dose limiting toxicities.^29,30

Kuhn has established critical academic and public-private-partnerships with the ultimate goal of HD-SCA to enable and motivate the necessary studies for clinical utility.  He has published over 200 peer scientific articles and several patents resulting from his research.

Kuhn is the original founder of Epic Sciences whose mission is to develop clinical solutions that accelerate drug development and guided therapy across cancer drug indications.^17,18 Epic's new AR-V7 CTC liquid biopsy test is the first clinically proven predictive test for metastatic castration-resistant prostate cancer which became available for prostate cancer care in June 2017.^31-33 (https://www.epicsciences.com/ar-v7-test/)

• Co-Chair, AACR Annual Meeting Program Committee, March 30 - April 3, 2019, Atlanta, Georgia

• Member, Internal Advisory Committee, Children’s Hospital-Los Angeles, 2018 – present

• Member, Cancer Science Committee, XPrize Foundation, 2018 - present

• Member, Translational Research Sub-Committee (Track), European Society of Medical (ESMO), 2018 - present
• Program Committee, American Association for Cancer Research (AACR), 2018 - present
• Co-Chair, AACR Think Tank in Convergent Science in Cancer, 2018 - 2019
• Member, Cancer Research UK, Early Detection Committee, 2017 – present
• Technology Corner Story, the Clinical Chemist, Finding Waldo: The Emerging Field of Circulating Tumor Cells, Vikram Sheel Kumar and Molly Webster, Clinical Chemistry 2014. DOI: 10.11373/clinchem.2014.233080
• Member, The Biomarkers Consortium, Foundation of the NIH, 2013 - present
• SWOG Breast Cancer Translational Science Working Group, 2013 - present        
• Top Ten Scientific Breakthroughs of 2007, Science Magazine (2007)
• Nominator, The Heinz Awards (12007, 2008)
• Distinguished Doctoral Dissertation Award (1996
• NATO grant to attend Advanced Study Institute, Erice (1996)
• Linus Pauling Award, American Crystallographic Association (1995)
• Linus Pauling Award, American Crystallographic Association (1994)

Kuhn is married with two children and currently resides in Southern California.

1. Peter Kuhn Faculty Profile, USC Dornsife, University of Southern California.
2. Peter Kuhn Keck School Faculty, Keck School of Medicine of USC.
3. Peter Kuhn, Faculty Profile, USC Michelson Center for Convergent Bioscience.
4. Redinbo MR, Stewart L, Kuhn P, Champoux JJ, and Hol WGJ.  Crystal Structures of Human Topoisomerase I in Covalent and Noncovalent Complexes with DNA. Science 1998; 279: 1504-1513.
5. “The power of fear drove cancer researcher Peter Kuhn toward his vocation. https://news.usc.edu/151856/the-power-of-fear-drove-cancer-researcher-peter-kuhn-toward-his-vocation/; November 23, 2018, USC News.
6. Genick U, Softis SM, Kuhn P, Canestrelli IL, and Getzoff ED.  Structure at 0.85 Å Resolution of an Early Protein Photocycle Intermediate.  Nature 1998;392:206-209.
7. Lesley SA, Kuhn P, Godzik A, Deacon AM, Mathews I, Kreusch A, Spraggon G, Klock HE, McMullan D, Shin T, Vincent J, Robb A, Brinen LS, Miller MD, McPhillips TM, Miller MA, Scheibe D, Canaves JM, Guda C, Jaroszewski L, Selby TL, Elsliger M-A, Wooley J, Taylor SS, Hodgson KO, Wilson IA, Schultz PG, Stevens RC. Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline. Proceedings of the National Academy of Sciences of the United States of America 2002;99:11664-69.
8.  Kuhn P, Wilson K, Patch MG and Stevens RC.  The genesis of high-throughput structure-based drug discovery using protein crystallography.  Current Opinion in Chemical Biology 2002;6:704-710. Bern M, Goldberg D, Stevens RC, Kuhn P. Automatic classification of protein crystallization images using a curve-tracking algorithm. J Appl Crystallogr 2004;37:279-287.
9. Peti W, Johnson MA, Herrmann T, Neuman BW, Buchmeier MJ, Nelson M, Joseph J, Page R, Stevens RC, Kuhn P, Wuthrich K. Structural genomics of the severe acute respiratory syndrome coronavirus: nuclear magnetic resonance structure of the protein nsP7.  J Virol 2005;79:12905-13.
10. Saikatendu KS, Joseph JS, Subramanian V, Clayton T, Griffith M, Moy K, Velasquez J, Neuman BW, Buchmeier MJ, Stevens RC, Kuhn P. Structural basis of severe acute respiratory syndrome coronavirus ADP-ribose-1''-phosphate dephosphorylation by a conserved domain of nsP3. Structure. 2005;13:1665-75.
11. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 2007;318:1258-65.
12. Wu B, Chien YET, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Jamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC. Structures of the CXCR4 Chemokine GPCR with Small –Molecule and Cyclic Peptide Antagonists. Science 2010;330:1066-1071.  
13. Marrinucci D, Bethel K, Luttgen M, Bruce, R, Nieva, J, Kuhn P. Circulating tumor cells from well-differentiated lung adenocarcinoma retain cytomorphologic features of primary tumor type. Archives of Pathology and Laboratory Medicine, 2009 133:1468-1471.
14. Marrinucci D, Bethel K, Lazar D, Fisher J, Huynh E, Clark P, Bruce R, Nieva J, Kuhn P. Cytomorphology of circulating colorectal tumor cells: a small case series. J Oncol 2010; 2010:861341.
15. Marrinucci D, Bethel K, Kolatkar A, Luttgen M, Malchiodi M, Baehring F, Voigt k, Lazar D, Nieva J, Bazhenova L, Ko AH, Korn WM, Schram E, Coward M, Yang X, Metzner T, Lamy R, Honnatti M, Yoshioka C, Kunken J, Petrova Y, Sok D, Nelson D, Kuhn P. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys Biol 2012;9: 016003.
16. Dago AE, Stepansky A, Carlsson A, Luttgen M, Kendall J, Basian T, Kolatkar A, Wigler M, Bethel K, Gross ME, Hicks J, Kuhn P. Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLoS One 2014;9:e101777.  
17. Fikes, Bradley J. (November 13, 2012). "Epic Sciences raises $13 million". San Diego Union Tribune.
18. Bigelow, Bruce (16 February 2012). "Xconomist of the Week: Peter Kuhn on Detecting Circulating Tumor Cells". Xconomy.
19. Gerdtsson E, Pore M, Thiele J-A, Sandstrom Gerdtsson A, Malihi PD, Nevarez R, Kolatkar A, Ruiz Velasco C, Wix S, Singh M, Carlsson A, Zurita AJ, Logothetis C, Merchant AA, Hicks J, Kuhn P.  Multiplex protein detection on circulating tumor cells from liquid biopsies using imaging mass cytometry. Converg Sci Phys Oncol 2018;4:015002.
20. Malihi P, Morikado M, Welter L, Liu ST, Miller ET, Cadaneanu RM, Knudsen BS, Lewis MS, Carlsson A, Ruiz Velasco C, Kolatkar A, Rodriguez-Lee M, Garraway IP, Hicks J, Kuhn P. Clonal diversity revealed by morphoproteomic and copy number profiles of single prostate cancer cells at diagnosis. Converg Sci Phys Oncol 2018;4:015003.
21. Rodriguez-Lee M, Kolatkar A, McCormick M, Dago, AE, Kendall J, Carlsson NA, Bethel K, Greenspan E, Hwang S, Waitman K, Nieva J, Hicks J, Kuhn P. Effect of blood collection tube type and time to processing on the enumeration and high-content characterization of circulating tumor cells using the high-definition single cell assay. Arch Pathol Lab Med 2018;142:198-207.
22. Carlsson A, Kuhn P, Luttgen MS, Dizon KK, Troncoso P, Corn PG, Kolatkar A, Hicks, JB, Logothetis C, Zurita AJ. Paired high-content analysis of prostate cáncer cells in bone marrow and blood characterizes increased androgen receptor expression in tumor cell clusters. Clin Cancer Rsch 2016;1355.2016.
23. Shishido SN, Carlsson A, Nieva J, Bethel K, Hicks JB, Bazhenova L, Kuhn P. Circulating tumor cells as a response monitor in stage IV non-small cell lung cancer. J Transl Med 2019 17:294-303.
24. Newton PK, Mason J, Hurt b, Bethel K, Bazhenova L, Nieva J, Kuhn P.  Entropy complexity, and Markov diagrams for random walk cancer models. Sci Rep 2014;4:7558.
25. Newton P, Mason J, Venkatappa N, Jochelson M, Hurt B, Nieva J, Comen E, Norton L, Kuhn P. Spatiotemporal Progression of Metastatic Breast Cancer: A Markov chain model highlighting the role of early metastatic sites. NPJ Breast Cancer 2015;1:15018. 
26. Hasnain Z, Mason J, Gill K, Miranda G, Gill IS, Newton PK, Kuhn P. Machine learning models for predicting post-cystectomy recurrence and survival in bladder cancer patients. PLOS One PLoS One 2019;14:e0210976.
27. Fuji T, Mason J, Chen A, Kuhn P, Woodward WA, Tripathy D, Newton PK, Ueno NT. Prediction of bone metastasis in inflammatory breat cancer using a Markov Chain Model. Oncologist 2019, Epub ahead of print.
28. Hasnain Z, Li M, Dorff T, Quinn D, Ueno NT, Yennu S, Kolatkar A, Shahabi C, Nocera L, Nieva J, Kuhn P, Newton PK. Low-dimensional dynamical characterization of human performance of cancer patients using motion data. Clin Biomech (Bristol, Avon) 2018;56:61-69.
29. Broderick J, May M, Schwartz JE, Li M, Mejia A, Nocera L, Kolatkar A, Ueno NT, Yennu S, Lee J, Hanlon S, Cozzens FA, Shahabi C, Kuhn P, Nieva J. Patient Reported Outcomes Can Improve Performance Status Assessment: A Pilot Study. J Patient Reported Outcomes 2019;3:41.
30. Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer. European Association of Urology 2017;71:874-882.
31. Scher HI, Graf RP, Schreiber NA, Jayaram A, Winquist E, McLaughlin B, Lu D, Fleisher M, Orr S, Lowes L, Anderson A, Wang Y, Dittamore R, Allan AL, Attard G, Heller G. Assessment of the validity of nuclear-localized androgen receptor splice variant 7 in circulating tumor cells as a predictive biomarker for castration-resistant prostate cancer. JAMA Oncol 2018;4:1179-1186.
32. Armstrong AJ, Halabi S, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ, Danila DC, Healy P, Anand M, Rothwell CJ, Rasmussen J, Thornburg B, Berry WR, Wilder RS, Lu C2, Chen Y, Silberstein JL, Kemeny G, Galletti G, Somarelli JA, Gupta S, Gregory SG, Scher HI, Dittamore R, Tagawa ST, Antonarakis ES, George DJ. Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study.J Clin Oncol 2019;37:1120-1129.