Program Official
Richard Mazurchuk, Ph.D.

Principal Investigator

Michael P.
Snyder
Awardee Organization

Stanford University
United States

Fiscal Year
2023
Activity Code
U2C
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
Notice of Funding Opportunity
NIH RePORTER
For more information, see NIH RePORTER Project 3U2CCA233311-01S1

Precancer Atlas of Familial Adenomatous Polyposis

We are building a Precancer Atlas of colorectal cancer from Familial Adenomatous Polyposis (FAP) patients. We have built a biobank containing thousands of samples from 78 donors. We have applied genomic, epigenomic, proteomic, lipidomic, metabolomic, transcriptomic, and spatial assays to characterize the molecular changes occurring during the progression from normal mucosa to cancer. We propose to use an integrated approach to further develop our Precancer Atlas. By profiling multiple polyps from the same patient, our Precancer Atlas enables characterization of the early events driving colorectal cancer. We will: 1) Complete procurement of longitudinal tissue samples from 100 donors during surveillance colonoscopy and during prophylactic surgical colectomy, including whole blood, serum, normal colonic tissue, colon microbiome, benign pre-cancerous polyps, dysplastic precancerous polyps and colon adenocarcinomas. The material will be used for our own center and will also be available to the Human Tumor Atlas Network (HTAN). Medical records, longitudinal samples and all relevant metadata will also be collected. 2) Characterize the tissue samples with state-of-the-art omics and imaging technologies. 3) Integrate results from -omics, imaging and medical information, to build a spatiotemporal, multidimensional, integrative multi-omics cancer atlas, and develop longitudinal and predictive models for PreCancer biology and progression. 4) Complete our establishment of multi-omics technologies, finishing our CODEX, snRNA-seq and organoid profiling. 5) Complete the publication of our “multiscale deep data analysis” on a large number of samples from a few people. Use this information to guide additional data collection, including our followup snRNA-seq experiments and our hypothesis-testing experiments in organoid models. 6) Identify factors (e.g. germline genetics, immune dysfunction) contributing to polyp heterogeneity and build disease progression models based on these data. 7) Make all biospecimens, information, protocols and software available to the PCA, HTAN and the general scientific community.

Publications

  • Haq ATA, Yang PP, Jin C, Shih JH, Chen LM, Tseng HY, Chen YA, Weng YS, Wang LH, Snyder MP, Hsu HL. Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer. Theranostics. 2024 Mar 3;14(5):2167-2189. doi: 10.7150/thno.92922. eCollection 2024. PMID: 38505617
  • Sanghi A, Gruber JJ, Metwally A, Jiang L, Reynolds W, Sunwoo J, Orloff L, Chang HY, Kasowski M, Snyder MP. Chromatin accessibility associates with protein-RNA correlation in human cancer. Nature communications. 2021 Sep 30;12(1):5732. PMID: 34593797
  • Cabruja M, Priotti J, Domizi P, Papsdorf K, Kroetz DL, Brunet A, Contrepois K, Snyder MP. In-depth triacylglycerol profiling using MS3 Q-Trap mass spectrometry. Analytica chimica acta. 2021 Nov 1;1184:339023. Epub 2021 Sep 3. PMID: 34625255
  • Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Nawy T, Hupalowska A, Rood JE, Ashenberg O, Cerami E, Coffey RJ, Demir E, Ding L, Esplin ED, Ford JM, Goecks J, Ghosh S, Gray JW, Guinney J, Hanlon SE, Hughes SK, Hwang ES, Iacobuzio-Donahue CA, Jané-Valbuena J, Johnson BE, Lau KS, Lively T, Mazzilli SA, Pe'er D, Santagata S, Shalek AK, Schapiro D, Snyder MP, Sorger PK, Spira AE, Srivastava S, Tan K, West RB, Williams EH, Human Tumor Atlas Network, Aberle D, Achilefu SI, Ademuyiwa FO, Adey AC, Aft RL, Agarwal R, Aguilar RA, Alikarami F, Allaj V, Amos C, Anders RA, Angelo MR, Anton K, Ashenberg O, Aster JC, Babur O, Bahmani A, Balsubramani A, Barrett D, Beane J, Bender DE, Bernt K, Berry L, Betts CB, Bletz J, Blise K, Boire A, Boland G, Borowsky A, Bosse K, Bott M, Boyden E, Brooks J, Bueno R, Burlingame EA, Cai Q, Campbell J, Caravan W, Cerami E, Chaib H, Chan JM, Chang YH, Chatterjee D, Chaudhary O, Chen AA, Chen B, Chen C, Chen CH, Chen F, Chen YA, Chheda MG, Chin K, Chiu R, Chu SK, Chuaqui R, Chun J, Cisneros L, Coffey RJ, Colditz GA, Cole K, Collins N, Contrepois K, Coussens LM, Creason AL, Crichton D, Curtis C, Davidsen T, Davies SR, de Bruijn I, Dellostritto L, De Marzo A, Demir E, DeNardo DG, Diep D, Ding L, Diskin S, Doan X, Drewes J, Dubinett S, Dyer M, Egger J, Eng J, Engelhardt B, Erwin G, Esplin ED, Esserman L, Felmeister A, Feiler HS, Fields RC, Fisher S, Flaherty K, Flournoy J, Ford JM, Fortunato A, Frangieh A, Frye JL, Fulton RS, Galipeau D, Gan S, Gao J, Gao L, Gao P, Gao VR, Geiger T, George A, Getz G, Ghosh S, Giannakis M, Gibbs DL, Gillanders WE, Goecks J, Goedegebuure SP, Gould A, Gowers K, Gray JW, Greenleaf W, Gresham J, Guerriero JL, Guha TK, Guimaraes AR, Guinney J, Gutman D, Hacohen N, Hanlon S, Hansen CR, Harismendy O, Harris KA, Hata A, Hayashi A, Heiser C, Helvie K, Herndon JM, Hirst G, Hodi F, Hollmann T, Horning A, Hsieh JJ, Hughes S, Huh WJ, Hunger S, Hwang SE, Iacobuzio-Donahue CA, Ijaz H, Izar B, Jacobson CA, Janes S, Jané-Valbuena J, Jayasinghe RG, Jiang L, Johnson BE, Johnson B, Ju T, Kadara H, Kaestner K, Kagan J, Kalinke L, Keith R, Khan A, Kibbe W, Kim AH, Kim E, Kim J, Kolodzie A, Kopytra M, Kotler E, Krueger R, Krysan K, Kundaje A, Ladabaum U, Lake BB, Lam H, Laquindanum R, Lau KS, Laughney AM, Lee H, Lenburg M, Leonard C, Leshchiner I, Levy R, Li J, Lian CG, Lim KH, Lin JR, Lin Y, Liu Q, Liu R, Lively T, Longabaugh WJR, Longacre T, Ma CX, Macedonia MC, Madison T, Maher CA, Maitra A, Makinen N, Makowski D, Maley C, Maliga Z, Mallo D, Maris J, Markham N, Marks J, Martinez D, Mashl RJ, Masilionais I, Mason J, Massagué J, Massion P, Mattar M, Mazurchuk R, Mazutis L, Mazzilli SA, McKinley ET, McMichael JF, Merrick D, Meyerson M, Miessner JR, Mills GB, Mills M, Mondal SB, Mori M, Mori Y, Moses E, Mosse Y, Muhlich JL, Murphy GF, Navin NE, Nawy T, Nederlof M, Ness R, Nevins S, Nikolov M, Nirmal AJ, Nolan G, Novikov E, Oberdoerffer P, O'Connell B, Offin M, Oh ST, Olson A, Ooms A, Ossandon M, Owzar K, Parmar S, Patel T, Patti GJ, Pe'er D, Pe'er I, Peng T, Persson D, Petty M, Pfister H, Polyak K, Pourfarhangi K, Puram SV, Qiu Q, Quintanal-Villalonga Á, Raj A, Ramirez-Solano M, Rashid R, Reeb AN, Regev A, Reid M, Resnick A, Reynolds SM, Riesterer JL, Rodig S, Roland JT, Rosenfield S, Rotem A, Roy S, Rozenblatt-Rosen O, Rudin CM, Ryser MD, Santagata S, Santi-Vicini M, Sato K, Schapiro D, Schrag D, Schultz N, Sears CL, Sears RC, Sen S, Sen T, Shalek A, Sheng J, Sheng Q, Shoghi KI, Shrubsole MJ, Shyr Y, Sibley AB, Siex K, Simmons AJ, Singer DS, Sivagnanam S, Slyper M, Snyder MP, Sokolov A, Song SK, Sorger PK, Southard-Smith A, Spira A, Srivastava S, Stein J, Storm P, Stover E, Strand SH, Su T, Sudar D, Sullivan R, Surrey L, Suvà M, Tan K, Terekhanova NV, Ternes L, Thammavong L, Thibault G, Thomas GV, Thorsson V, Todres E, Tran L, Tyler M, Uzun Y, Vachani A, Van Allen E, Vandekar S, Veis DJ, Vigneau S, Vossough A, Waanders A, Wagle N, Wang LB, Wendl MC, West R, Williams EH, Wu CY, Wu H, Wu HY, Wyczalkowski MA, Xie Y, Yang X, Yapp C, Yu W, Yuan Y, Zhang D, Zhang K, Zhang M, Zhang N, Zhang Y, Zhao Y, Zhou DC, Zhou Z, Zhu H, Zhu Q, Zhu X, Zhu Y, Zhuang X. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell. 2020 Apr 16;181(2):236-249. PMID: 32302568
  • Schapiro D, Yapp C, Sokolov A, Reynolds SM, Chen YA, Sudar D, Xie Y, Muhlich J, Arias-Camison R, Arena S, Taylor AJ, Nikolov M, Tyler M, Lin JR, Burlingame EA, Human Tumor Atlas Network, Chang YH, Farhi SL, Thorsson V, Venkatamohan N, Drewes JL, Pe'er D, Gutman DA, Herrmann MD, Gehlenborg N, Bankhead P, Roland JT, Herndon JM, Snyder MP, Angelo M, Nolan G, Swedlow JR, Schultz N, Merrick DT, Mazzili SA, Cerami E, Rodig SJ, Santagata S, Sorger PK, Abravanel DL, Achilefu S, Ademuyiwa FO, Adey AC, Aft R, Ahn KJ, Alikarami F, Alon S, Ashenberg O, Baker E, Baker GJ, Bandyopadhyay S, Bayguinov P, Beane J, Becker W, Bernt K, Betts CB, Bletz J, Blosser T, Boire A, Boland GM, Boyden ES, Bucher E, Bueno R, Cai Q, Cambuli F, Campbell J, Cao S, Caravan W, Chaligné R, Chan JM, Chasnoff S, Chatterjee D, Chen AA, Chen C, Chen CH, Chen B, Chen F, Chen S, Chheda MG, Chin K, Cho H, Chun J, Cisneros L, Coffey RJ, Cohen O, Colditz GA, Cole KA, Collins N, Cotter D, Coussens LM, Coy S, Creason AL, Cui Y, Zhou DC, Curtis C, Davies SR, Bruijn I, Delorey TM, Demir E, Denardo D, Diep D, Ding L, DiPersio J, Dubinett SM, Eberlein TJ, Eddy JA, Esplin ED, Factor RE, Fatahalian K, Feiler HS, Fernandez J, Fields A, Fields RC, Fitzpatrick JAJ, Ford JM, Franklin J, Fulton B, Gaglia G, Galdieri L, Ganesh K, Gao J, Gaudio BL, Getz G, Gibbs DL, Gillanders WE, Goecks J, Goodwin D, Gray JW, Greenleaf W, Grimm LJ, Gu Q, Guerriero JL, Guha T, Guimaraes AR, Gutierrez B, Hacohen N, Hanson CR, Harris CR, Hawkins WG, Heiser CN, Hoffer J, Hollmann TJ, Hsieh JJ, Huang J, Hunger SP, Hwang ES, Iacobuzio-Donahue C, Iglesia MD, Islam M, Izar B, Jacobson CA, Janes S, Jayasinghe RG, Jeudi T, Johnson BE, Johnson BE, Ju T, Kadara H, Karnoub ER, Karpova A, Khan A, Kibbe W, Kim AH, King LM, Kozlowski E, Krishnamoorthy P, Krueger R, Kundaje A, Ladabaum U, Laquindanum R, Lau C, Lau KSK, LeBoeuf NR, Lee H, Lenburg M, Leshchiner I, Levy R, Li Y, Lian CG, Liang WW, Lim KH, Lin Y, Liu D, Liu Q, Liu R, Lo J, Lo P, Longabaugh WJ, Longacre T, Luckett K, Ma C, Maher C, Maier A, Makowski D, Maley C, Maliga Z, Manoj P, Maris JM, Markham N, Marks JR, Martinez D, Mashl J, Masilionis I, Massague J, Mazurowski MA, McKinley ET, McMichael J, Meyerson M, Mills GB, Mitri ZI, Moorman A, Mudd J, Murphy GF, Deen NNA, Navin NE, Nawy T, Ness RM, Nevins S, Nirmal AJ, Novikov E, Oh ST, Oldridge DA, Owzar K, Pant SM, Park W, Patti GJ, Paul K, Pelletier R, Persson D, Petty C, Pfister H, Polyak K, Puram SV, Qiu Q, Villalonga ÁQ, Ramirez MA, Rashid R, Reeb AN, Reid ME, Remsik J, Riesterer JL, Risom T, Ritch CC, Rolong A, Rudin CM, Ryser MD, Sato K, Sears CL, Semenov YR, Shen J, Shoghi KI, Shrubsole MJ, Shyr Y, Sibley AB, Simmons AJ, Sinha A, Sivagnanam S, Song SK, Southar-Smith A, Spira AE, Cyr JS, Stefankiewicz S, Storrs EP, Stover EH, Strand SH, Straub C, Street C, Su T, Surrey LF, Suver C, Tan K, Terekhanova NV, Ternes L, Thadi A, Thomas G, Tibshirani R, Umeda S, Uzun Y, Vallius T, Van Allen ER, Vandekar S, Vega PN, Veis DJ, Vennam S, Verma A, Vigneau S, Wagle N, Wahl R, Walle T, Wang LB, Warchol S, Washington MK, Watson C, Weimer AK, Wendl MC, West RB, White S, Windon AL, Wu H, Wu CY, Wu Y, Wyczalkowski MA, Xu J, Yao L, Yu W, Zhang K, Zhu X. MITI minimum information guidelines for highly multiplexed tissue images. Nature methods. 2022 Mar;19(3):262-267. PMID: 35277708
  • Li Y, Zhang S, Snyder MP, Meador KJ. Precision medicine in women with epilepsy: The challenge, systematic review, and future direction. Epilepsy & behavior : E&B. 2021 May;118:107928. Epub 2021 Mar 25. PMID: 33774354
  • Baskar R, Chen AF, Favaro P, Reynolds W, Mueller F, Borges L, Jiang S, Park HS, Kool ET, Greenleaf WJ, Bendall SC. Integrating transcription-factor abundance with chromatin accessibility in human erythroid lineage commitment. Cell reports methods. 2022 Mar 28;2. (3). Epub 2022 Mar 21. PMID: 35463156
  • Granja JM, Corces MR, Pierce SE, Bagdatli ST, Choudhry H, Chang HY, Greenleaf WJ. ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis. Nature genetics. 2021 Mar;53(3):403-411. Epub 2021 Feb 25. PMID: 33633365
  • Erwin GS, Gürsoy G, Al-Abri R, Suriyaprakash A, Dolzhenko E, Zhu K, Hoerner CR, White SM, Ramirez L, Vadlakonda A, Vadlakonda A, von Kraut K, Park J, Brannon CM, Sumano DA, Kirtikar RA, Erwin AA, Metzner TJ, Yuen RKC, Fan AC, Leppert JT, Eberle MA, Gerstein M, Snyder MP. Recurrent repeat expansions in human cancer genomes. Nature. 2023 Jan;613(7942):96-102. Epub 2022 Dec 14. PMID: 36517591
  • Gaddameedi JD, Chou T, Geller BS, Rangarajan A, Swaminathan TA, Dixon D, Long K, Golder CJ, Vuong VA, Banuelos S, Greenhouse R, Snyder MP, Lipchik AM, Gruber JJ. Acetyl-Click Screening Platform Identifies Small-Molecule Inhibitors of Histone Acetyltransferase 1 (HAT1). Journal of medicinal chemistry. 2023 Apr 27;66(8):5774-5801. Epub 2023 Apr 7. PMID: 37027002
  • Ghorasaini M, Mohammed Y, Adamski J, Bettcher L, Bowden JA, Cabruja M, Contrepois K, Ellenberger M, Gajera B, Haid M, Hornburg D, Hunter C, Jones CM, Klein T, Mayboroda O, Mirzaian M, Moaddel R, Ferrucci L, Lovett J, Nazir K, Pearson M, Ubhi BK, Raftery D, Riols F, Sayers R, Sijbrands EJG, Snyder MP, Su B, Velagapudi V, Williams KJ, de Rijke YB, Giera M. Cross-Laboratory Standardization of Preclinical Lipidomics Using Differential Mobility Spectrometry and Multiple Reaction Monitoring. Analytical chemistry. 2021 Dec 14;93(49):16369-16378. Epub 2021 Dec 3. PMID: 34859676
  • Alseekh S, Aharoni A, Brotman Y, Contrepois K, D'Auria J, Ewald J, C Ewald J, Fraser PD, Giavalisco P, Hall RD, Heinemann M, Link H, Luo J, Neumann S, Nielsen J, Perez de Souza L, Saito K, Sauer U, Schroeder FC, Schuster S, Siuzdak G, Skirycz A, Sumner LW, Snyder MP, Tang H, Tohge T, Wang Y, Wen W, Wu S, Xu G, Zamboni N, Fernie AR. Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices. Nature methods. 2021 Jul;18(7):747-756. Epub 2021 Jul 8. PMID: 34239102
  • Becker WR, Nevins SA, Chen DC, Chiu R, Horning AM, Guha TK, Laquindanum R, Mills M, Chaib H, Ladabaum U, Longacre T, Shen J, Esplin ED, Kundaje A, Ford JM, Curtis C, Snyder MP, Greenleaf WJ. Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer. Nature genetics. 2022 Jul;54(7):985-995. Epub 2022 Jun 20. PMID: 35726067