James Fraser, PhD

james.jpg
Department Chair and Professor
Bioengineering
[email protected]
+1 415 493-8421

The long-term goals of our research are to understand how protein conformational ensembles are reshaped by perturbations, such as mutation and ligand binding, and to quantify how these perturbations impact protein function and organismal fitness. To accomplish these goals, we create new computational and biophysical approaches to study how proteins move between different conformational states. As a graduate student, with Tom Alber at UC Berkeley, James established room temperature X-ray data collection techniques and electron density sampling strategies to define protein conformational ensembles essential for catalysis. Prior to starting an independent position at UCSF, he was a visiting EMBO Short Term Fellow in the lab of Dan Tawfik at the Weizmann Institute of Science in Israel and developed expertise in directed evolution and high-throughput assays of enzymatic or binding activity. In 2011, James started his independent research career as a QB3 at UCSF Fellow and in 2013 was appointed as an Assistant Professor of Bioengineering and Therapeutic Sciences. At UCSF, his lab continue to pioneer new methods for extracting the maximal information from X-ray diffraction experiments and electron density maps. Additionally, the group uses two complementary approaches to study the relationship between protein conformational ensembles and function. To dissect consequences of mutations on organismal fitness, we use high-throughput systems biology and biophysical methods to analyze large sets of clinically or biophysically interesting mutations. To improve our ability to engineer new protein functions, we investigate changes to the conformational ensemble as new enzymatic and binding functions emerge from directed evolution studies.

Publications

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

bioRxiv : the preprint server for biology

Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Zapatero-Belinchón FJ, McCavitt-Malvido M, Doruk YU, Stevens MGV, Diolati ME, Jogalekar MP, Richards AL, Montano M, Rosecrans J, Matthay M, Togo T, Gonciarz RL, Gopalkrishnan S, Neitz RJ, Krogan NJ, Swaney DL, Shoichet BK, Ott M, Renslo AR, Ashworth A, Fraser JS

Recommendations for accelerating open preprint peer review to improve the culture of science.

PLoS biology

Avissar-Whiting M, Belliard F, Bertozzi SM, Brand A, Brown K, Clément-Stoneham G, Dawson S, Dey G, Ecer D, Edmunds SC, Farley A, Fischer TD, Franko M, Fraser JS, Funk K, Ganier C, Harrison M, Hatch A, Hazlett H, Hindle S, Hook DW, Hurst P, Kamoun S, Kiley R, Lacy MM, LaFlamme M, Lawrence R, Lemberger T, Leptin M, Lumb E, MacCallum CJ, Marcum CS, Marinello G, Mendonça A, Monaco S, Neves K, Pattinson D, Polka JK, Puebla I, Rittman M, Royle SJ, Saderi D, Sever R, Shearer K, Spiro JE, Stern B, Taraborelli D, Vale R, Vasquez CG, Waltman L, Watt FM, Weinberg ZY, Williams M

Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Ka inhibitor that decouples anti-tumor activity from hyperinsulinemia.

Cancer discovery

Varkaris A, Pazolli E, Gunaydin H, Wang Q, Pierce L, Boezio AA, DiPietro L, Frost A, Giordanetto F, Hamilton EP, Harris K, Holliday M, Hunter TL, Iskandar A, Ji Y, Larivée A, LaRochelle JR, Lescarbeau A, Llambi F, Lormil B, Mader MM, Mar BG, Martin I, McLean TH, Michelsen K, Pechersky Y, Puente-Poushnejad E, Samadani R, Schram AM, Shortsleeves K, Swaminathan S, Tajmir S, Tan G, Tang Y, Valverde R, Wehrenberg B, Wilbur J, Williams BR, Zeng H, Walters WP, Wolf BB, Shaw DE, Bergstrom DA, Watters J, Fraser JS, Fortin PD, Kipp DR

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

The Journal of Immunology

Roberto R Ricardo-Gonzalez, Maya E Kotas, Claire O’Leary, Iliana Tenvooren, Diana Marquez, Katelyn Singh, William Damsky, Chang Liao, Andrew Schroeder, Jarish Cohen, Marlys S Fassett, Jinwoo Lee, Scott G Daniel, Kyle Bittinger, Roberto Efrain Diaz, James Fraser, Karl Mark Ansel, Matthew Spitzer, Hong-Erh Liang, Richard M Locksley

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

Research square

Verba K, Gupta M, Azumaya C, Moritz M, Pourmal S, Diallo A, Merz G, Jang G, Bouhaddou M, Fossati A, Brilot A, Diwanji D, Hernandez E, Herrera N, Kratochvil H, Lam V, Li F, Li Y, Nguyen H, Nowotny C, Owens T, Peters J, Rizo A, Schulze-Gahmen U, Smith A, Young I, Yu Z, Asarnow D, Billesbølle C, Campbell M, Chen J, Chen KH, Chio US, Dickinson M, Doan L, Jin M, Kim K, Li J, Li YL, Linossi E, Liu Y, Lo M, Lopez J, Lopez K, Mancino A, Iii FM, Paul M, Pawar K, Pelin A, Pospiech T, Puchades C, Remesh S, Safari M, Schaefer K, Sun M, Tabios M, Thwin A, Titus E, Trenker R, Tse E, Tsui TKM, Feng F, Zhang K, Zhang Y, Zhao J, Zhou F, Zhou Y, Zuliani-Alvarez L, Agard D, Cheng Y, Fraser J, Jura N, Kortemme T, Manglik A, Southworth D, Stroud R, Swaney D, Krogan N, Frost A, Rosenberg O

Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge.

Nature methods

Lawson CL, Kryshtafovych A, Adams PD, Afonine PV, Baker ML, Barad BA, Bond P, Burnley T, Cao R, Cheng J, Chojnowski G, Cowtan K, Dill KA, DiMaio F, Farrell DP, Fraser JS, Herzik MA, Hoh SW, Hou J, Hung LW, Igaev M, Joseph AP, Kihara D, Kumar D, Mittal S, Monastyrskyy B, Olek M, Palmer CM, Patwardhan A, Perez A, Pfab J, Pintilie GD, Richardson JS, Rosenthal PB, Sarkar D, Schäfer LU, Schmid MF, Schröder GF, Shekhar M, Si D, Singharoy A, Terashi G, Terwilliger TC, Vaiana A, Wang L, Wang Z, Wankowicz SA, Williams CJ, Winn M, Wu T, Yu X, Zhang K, Berman HM, Chiu W

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

Science (New York, N.Y.)

Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Nature

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

IUCrJ

Wolff AM, Young ID, Sierra RG, Brewster AS, Martynowycz MW, Nango E, Sugahara M, Nakane T, Ito K, Aquila A, Bhowmick A, Biel JT, Carbajo S, Cohen AE, Cortez S, Gonzalez A, Hino T, Im D, Koralek JD, Kubo M, Lazarou TS, Nomura T, Owada S, Samelson AJ, Tanaka T, Tanaka R, Thompson EM, van den Bedem H, Woldeyes RA, Yumoto F, Zhao W, Tono K, Boutet S, Iwata S, Gonen T, Sauter NK, Fraser JS, Thompson MC

Co-occurring alterations in the RAS-MAPK pathway limit response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Rotow JK, Gui P, Wu W, Raymond VM, Lanman RB, Kaye FJ, Peled N, Fece de la Cruz F, Nadres B, Corcoran RB, Yeh I, Bastian BC, Starostik P, Newsom K, Olivas V, Wolff AM, Fraser JS, Collisson EA, McCoach CE, Camidge DR, Pacheco J, Bazhenova L, Li T, Bivona TG, Blakely CM

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance.

Biology open

Mavor D, Barlow KA, Asarnow D, Birman Y, Britain D, Chen W, Green EM, Kenner LR, Mensa B, Morinishi LS, Nelson CA, Poss EM, Suresh P, Tian R, Arhar T, Ary BE, Bauer DP, Bergman ID, Brunetti RM, Chio CM, Dai SA, Dickinson MS, Elledge SK, Helsell CVM, Hendel NL, Kang E, Kern N, Khoroshkin MS, Kirkemo LL, Lewis GR, Lou K, Marin WM, Maxwell AM, McTigue PF, Myers-Turnbull D, Nagy TL, Natale AM, Oltion K, Pourmal S, Reder GK, Rettko NJ, Rohweder PJ, Schwarz DMC, Tan SK, Thomas PV, Tibble RW, Town JP, Tsai MK, Ugur FS, Wassarman DR, Wolff AM, Wu TS, Bogdanoff D, Li J, Thorn KS, O'Conchúir S, Swaney DL, Chow ED, Madhani HD, Redding S, Bolon DN, Kortemme T, DeRisi JL, Kampmann M, Fraser JS

SCIENTIFIC COMMUNITY. Preprints for the life sciences.

Science (New York, N.Y.)

Berg JM, Bhalla N, Bourne PE, Chalfie M, Drubin DG, Fraser JS, Greider CW, Hendricks M, Jones C, Kiley R, King S, Kirschner MW, Krumholz HM, Lehmann R, Leptin M, Pulverer B, Rosenzweig B, Spiro JE, Stebbins M, Strasser C, Swaminathan S, Turner P, Vale RD, VijayRaghavan K, Wolberger C

Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting.

eLife

Mavor D, Barlow K, Thompson S, Barad BA, Bonny AR, Cario CL, Gaskins G, Liu Z, Deming L, Axen SD, Caceres E, Chen W, Cuesta A, Gate RE, Green EM, Hulce KR, Ji W, Kenner LR, Mensa B, Morinishi LS, Moss SM, Mravic M, Muir RK, Niekamp S, Nnadi CI, Palovcak E, Poss EM, Ross TD, Salcedo EC, See SK, Subramaniam M, Wong AW, Li J, Thorn KS, Conchúir SÓ, Roscoe BP, Chow ED, DeRisi JL, Kortemme T, Bolon DN, Fraser JS

Data publication with the structural biology data grid supports live analysis.

Nature communications

Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Fromme JC, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P

High-density grids for efficient data collection from multiple crystals.

Acta crystallographica. Section D, Structural biology

Baxter EL, Aguila L, Alonso-Mori R, Barnes CO, Bonagura CA, Brehmer W, Brunger AT, Calero G, Caradoc-Davies TT, Chatterjee R, Degrado WF, Fraser JS, Ibrahim M, Kern J, Kobilka BK, Kruse AC, Larsson KM, Lemke HT, Lyubimov AY, Manglik A, McPhillips SE, Norgren E, Pang SS, Soltis SM, Song J, Thomaston J, Tsai Y, Weis WI, Woldeyes RA, Yachandra V, Yano J, Zouni A, Cohen AE