Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

Kojo Elenitoba-Johnson, MD Memorial Sloan Kettering Cancer Center Dr. Elenitoba-Johnson is the inaugural Chair of the Department of Pathology and Laboratory Medicine, and Member of the Human Oncology & Pathogenesis Program (HOPP) at Memorial Sloan Kettering Cancer Center. Prior to this appointment, he was the Director of the Center of Personalized Diagnostics, and the inaugural Peter C. Nowell, M.D., Endowed Professor, in the Department of Pathology and Laboratory Medicine at Penn Medicine, Perelman School of Medicine, at the University of Pennsylvania from 2015 to August 2022. He is a recognized pioneer in lymphoma proteomics, and a top leader in precision and integrated diagnostics. His work is notable for the identification and mechanistic elucidation of targetable genetic alterations underlying the pathogenesis of specific lymphoma subtypes. Dr. Elenitoba-Johnson has contributed to over 180 peer-reviewed manuscripts, numerous chapters and text books. His research is supported by 3 RO1 awards from the National Institutes of Health. Dr. Elenitoba-Johnson is an elected member of the National Academy of Medicine, the American Society for Clinical Investigation and the International Lymphoma Study Group. (2017) and has been recognized with numerous professional honors and awards, notably the Ramzi Cotran Young Investigator Award from the United States and Canadian Academy of Pathology, the Outstanding Investigator (Former Warner-Lambert-Parke Davis) Award from the American Society for Investigative Pathology and the William Gerald Award from Memorial Sloan Kettering Cancer Center.

Declaration of Competing Interests

Dr. Elenitoba-Johnson declares no conflicts of interest.

Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

Wiebke Arlt, MD DSc FRCP FMedSci Medical Research Council Laboratory of Medical Sciences Wiebke Arlt is the Director of the Medical Research Council Laboratory of Medical Sciences (LMS) and Professor of Transdisciplinary Medicine at Imperial College London; she also serves as Honorary Consultant Endocrinologist at Imperial College Healthcare Trust, with a clinical focus on adrenal and reproductive endocrinology. At the LMS, she leads a multi-disciplinary research group comprising biochemists, clinician scientists and computational biologists, investigating the role of steroids in health and disease, with a focus on the link between steroids and metabolism. Her group uses steroid mass spectrometry in combination with in vitro, ex vivo and in vivo phenotyping in humans as a discovery tool and for the development of biomarkers utilised for diagnostic and prognostic test purposes. Wiebke has published over 250 original research articles and is a sought-after lecturer. Her scientific work has attracted major international prizes, most recently the 2021 Keith Harrison Memorial Lecture of the Endocrine Society of Australia, the 2019 Outstanding Clinical Investigator Award of the Endocrine Society USA, the 2017 Berthold Medal of the German Endocrine Society, and the 2016 Clinical Endocrinology Trust Medal of the European Society of Endocrinology. She was elected Fellow of the UK Academy of Medical Sciences in 2010 and currently serves on the Academy’s Council.

I will discuss steroid metabolomics, the combination of mass spectrometry-based steroid profiling with machine learning-based steroid data analysis. I will provide two clinically relevant examples: (1) the development of a new diagnostic biomarker test for the detection of adrenal cancer, with a timeline covering the last 15 years and including discovery, optimisation and prospective validation - adrenal cancer is rare but regularly discovered upon the investigation of incidentally discovered adrenal nodules, which are detected in 5% of all cross-sectional imaging scans; (2) the exploration of the steroid metabolome in a large comprehensively phenotyped cohort of newly diagnosed and treatment naïve women with polycystic ovary syndrome (PCOS), a condition affecting 10-15% of women worldwide and associated with significantly increased metabolic disease risk. Showing our data from this cohort, I will describe the potential of steroid metabolomics for detailed phenotyping, mechanistic exploration, prognostic prediction and therapeutic stratification in this underserved population.

Declaration of Competing Interests

Dr. Arlt declares no conflicts of interest.

Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

R. Graham Cooks, PhD Purdue University R. Graham Cooks is the Henry Bohn Hass Distinguished Professor in the Department of Chemistry at Purdue University. He has served as major professor to 150 PhD students. Dr. Cooks’ was a pioneer in the conception and implementation of tandem mass spectrometry (MS/MS) and of desorption ionization, especially molecular secondary ionization mass spectrometry (SIMS). His work also includes the development of miniature portable mass spectrometers using ambient ionization and application of this combination to problems of trace chemical analysis at point-of-care. His interests in the fundamentals of ion chemistry focus on chiral analysis based on the kinetics of cluster ion fragmentation. His group also studies collisions of ions at surfaces for new methods of molecular surface tailoring and analysis, and nanomaterials preparation by soft-landing of ions and charged droplets. Dr. Cooks also launched new methods of small scale synthesis based on accelerated reactions in microdroplets and incorporated this capability into high throughput screening instrumentation based on DESI. This screening capability extends to enzyme assays. Dr. Cooks has been recognized with the Mass Spectrometry and the Analytical Chemistry awards of the American Chemical Society, the Robert Boyle Medal and the Centennial Prize of the Royal Society of Chemistry, and the Camille & Henry Dreyfus Prize in the Chemical Sciences. He is an elected fellow of the American Academy of Arts and Sciences, the Academy of Inventors and the U.S. National Academy of Sciences.

R. Graham Cooks^1,2, Nicolás Morato^1,2, Andrew Mesecar^1,3
1Department of Chemistry, ²Department of Biochemistry, and ³Purdue Institute for Cancer Research, Purdue University. West Lafayette, IN 47907

This talk covers an as-yet-unfinished journey. It describes a suite of methods and instrumentation that is the work of many individuals over a long period. Applications to diagnostics, especially intraoperative diagnostics, are ongoing for brain and other cancers. The long view espoused here, describes a series of steps that stretches from half-century old mass spectrometry to new drug candidates, specifically for the case of prostate cancer.

1. MS and MS/MS: because mass spectrometry (MS) is a well suited to characterizing organic compounds, it can be used to characterize complex mixtures, provided sample ionization produces a corresponding mixture of molecular ions. This 1:1 transformation (molecule -> molecular ion) was first achieved by the then-new method of chemical ionization. This allowed two stages of mass analysis, MS/MS, to became an alternative to GC/MS (and later to LC/MS) for mixture analysis.[1]

2. Ambient ionization: the simplest, most direct form of MS, ionizes objects/materials/samples in the open air. Electrospray ionization provided the lead on atmospheric pressure ionization, but ambient ionization [2] goes further and avoids sample manipulation or purification. Desorption electrospray ionization (DESI) effects ionization by localized solvent extraction.[3]

3. MS imaging: any directed ionizing agent (ions in SIMS, neutrals in FAB, photons in LDI, droplets in DESI) is inherently an imaging method.[4]

4. Biomarker discovery: Comparisons of diseased and healthy tissue point to potential biomarkers, e.g. DESI MS/MS analysis of prostate tissue showed preferential localization of cholesterol sulfate in diseased tissue.[5].

5. Target validation: knockdown studies established an association of cholesterol sulfate transferase with prostate cancer.[6]

6. Late stage functionalization: High throughput DESI instrumentation [7] uses accelerated reactions in microdroplets [8,9] to synthesize large numbers of new drug candidates on the millisecond time scale.[10]

7. Enzyme inhibition: Collection of the functionalized products followed by enzyme kinetic measurements [10] validated inhibition for several particular compounds as potential prostate cancer drugs. 8. Animal, safety and efficacy studies lie in the future.

Support from NCATS and Waters, Inc. is gratefully acknowledged.

[1] R. W. Kondrat and R. G. Cooks, Anal. Chem. 50 (1978) 81A
[2] R. Graham Cooks, Zheng Ouyang, Zoltan Takats, Justin M. Wiseman, Science, 311 (2006) 1566-1570
[3] Zoltán Takáts, Justin Wiseman, Bogdan Gologan and R. Graham Cooks, Science, 306 (2004) 471 – 473
[4] Justin M. Wiseman, Demian R. Ifa, Qingyu Song, R. Graham Cooks”, Angew. Chem. Int. Ed. 45 (2006) 7188 – 7192
[5] Livia S. Eberlin; Allison L. Dill; Anthony B. Costa; Demian R. Ifa; Liang Cheng; Timothy Masterson; Michael Koch; Timothy L. Ratliff; R. Graham Cooks, Anal. Chem., 82 (2010) 3430–3434
[6] Renee E Vickman, Scott A. Crist, Kevin Kerian, Livia Eberlin, R. Graham Cooks, Grant N. Burcham, Kimberly K Buhman, Chang-Deng Hu, Andrew D. Mesecar, Laing Cheng and Timothy Ratliff, Mol. Cancer Res. 14 (2016) 776 – 786
[7] Michael Wleklinski, Bradley P. Loren, Christina R. Ferreira, Zinia Jaman, Larisa Avramova, Tiago J. P. Sobreira, David H. Thompson and R. Graham Cooks, Chem. Sci. 9 (2018) 1647 – 1653
[8] Xin Yan, Ryan M. Bain, and R. Graham Cooks Angew. Chem. Int. Ed. 55 (2016) 12960-12972
[9] R. Graham Cooks, Yunfei Feng, Kai-Hung Huang, Nicolás M. Morato, and Lingqi Qiu, Israel J. Chem. 63 (2023) e202300034
[10] Kai-Hung Huang, Nicolás M. Morato, Yunfei Feng, and R. Graham Cooks Angew. Chem. (2023) e202300956

Declaration of Competing Interests

The Cooks lab receives grant support from Waters.

Location: Steinbeck 1 (Conference Ctr > 2nd Floor)

Location: Steinbeck 2 (Conference Ctr > 2nd Floor)

Location: Steinbeck 3 (Conference Ctr > 2nd Floor)

Location: Colton (Conference Ctr > 2nd Floor)

Location: De Anza 1 (Portola Hotel > Ground Floor)

Location: Steinbeck 1 (Conference Ctr > 2nd Floor)

Location: Steinbeck 2 (Conference Ctr > 2nd Floor)

Location: Steinbeck 3 (Conference Ctr > 2nd Floor)

Location: Colton (Conference Ctr > 2nd Floor)

Location: De Anza 1 (Portola Hotel > Ground Floor)