Alejandro Chavez, M.D., Ph.D.

Alejandro Chavez, M.D., Ph.D.

Research Interest

Overview of Research

Our research group strives to push the boundaries of biotechnology and genetic engineering by developing new methods with which to modify, regulate, and probe eukaryotic genomes. We have a strong interest in drug development and neurodegeneration, and have created several novel technologies which we are currently applying in these areas.

Our work employs a variety of techniques ranging from oligo chip synthesis and library-based screening to iPS cell differentiation and live-cell imaging. We utilize a variety of model systems ranging from yeast to human cell culture and animal studies.

Our team places a strong emphasis on mentoring, and values the opportunity to be able to train the next generation of budding scientists.

  • BA, 2004 Genetics and Molecular Biology, Northwestern University
  • MD, PhD, 2011 Cell and Molecular Biology, University of Pennsylvania - School of Medicine
  • Residency: 2014 Massachuetts General Hospital
  • Fellowship: 2017 Massachusettes General Hospital

Church, G.M., Vora, S., Chavez, A., Chen, J., Pruitt, B. 2017. Methods of Modulating Expression of Target Nucleic Acid Sequences in a Cell. U.S. Patent Application 62/470,538, filed March 13, 2017. Patent Pending

Guo, X., Kaas, C., and Chavez, A. 2016. Methods of genetically altering yeast to produce yeast variants. U.S. Patent Application 62/396,395, filed September 19, 2016. Patent Pending

Kaas, C., and Chavez, A. 2016. Methods for screening using barcoded libraries. U.S. Patent Application 62/358,878, filed July 6, 2016. Patent Pending

Guo, X., Chavez, A., Schubert, M., and Kelsic E. 2016. Library-scale engineering of metabolic pathways. U.S. Patent Application 62/348,438, filed June 10, 2016. Patent Pending

Esvelt, K.M., Min, J., Noble, C.M., Buchthal, J., Chavez, A. 2016. Methods to design and use gene drives. U.S. Patent Application 62/333,580, filed May 9, 2016. Patent Pending

Chavez, A. 2016. Mutant cas proteins. U.S. Patent Application 62/310,018, filed March 18, 2016. Patent Pending

Chavez, A., and Pruitt, B.W., 2015. Cas discrimination using tuned guide RNA. U.S. Patent Application 62/266,851, filed December 14, 2015. Patent Pending

Hu, J., and Chavez, A., 2015. Methods of making guide RNA. U.S. Patent Application 62/220,524, filed September 19, 2015. Patent Pending

Chavez, A., and Tuttle, M., 2015. Cas9 genome editing and transcriptional regulation. U.S. Patent Application 62/200,303, filed August 3, 2015. Patent Pending.

Chavez, A., Poelwijk F., and Church G.M., 2013. Mutant Cas9 proteins. U.S. Patent 9,074,199, granted July 7, 2015

Member of Scientific Advisory Board, Addgene, Cambridge MA

Ad-hoc Reviewer for: Nature Communications, Nucleic Acid Research, ACS Synthetic Biology, Genome Biology

Recipient of 2017-2021 Burroughs Wellcome Career Award for Medical Scientist

02/2017 - Society for Laboratory Automation and Screening (SLAS) Tony B. Academic Travel Award

06/2016 - Poster of Distinction, Harvard Medical School Pathology Annual Retreat

2012 & 2013 - 1st place, Massachusetts General Hospital, Best Clinical Pathology Conference Talk

2013 - Chief Resident, Clinical Pathology, Massachusetts General Hospital

06/2011 - Morton McCutcheon Memorial Prize for meritorious laboratory research, UPenn

# denotes co-first author

^ denotes co-second author

* denotes co-senior author


#Guo, X., *#Chavez, A., #Tung, A., Chan, Y., Kaas, C., Yin, Y., Cecchi, R., Garnier, S.L., Kelsic, E.D., Schubert, M., DiCarlo, J.E., Collins, J.J., *Church, G.M., High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR–Cas9 in yeast. Nature Biotechnology. 2018; doi:10.1038/nbt.4147.

Chan, Y., Chan, Y.K., Goodman, D.B., Guo, X., Chavez, A., Lim, E.T., Church, G.M., Enabling multiplexed testing of pooled donor cells through whole-genome sequencing. Genome medicine 10 (1), 31.

Bester, A.C., ^Lee, J.D., ^Chavez, A., Lee, Y-R., Nachmani, D., Vora, S., Victor, J., Sauvageau, M., Monteleone, E., Rinn, J.L., Provero, P., Church, G.M., Clohessy, J.G., Pandolfi, P.P. An Integrated Genome Wide CRISPRa Approach to Functionalize lncRNAs in Drug Resistance. Cell. 2018; 173 (3), 649-664. e20

*#Chavez, A., #Pruitt, B.W., Tuttle, M., Shapiro, R.S., Cecchi, R.J., Winston, J., Turczyk, B.M., Tung, M., Collins, J.J., and Church, G.M*. Precise Cas9 targeting enables genomic mutation prevention. PNAS. 2018; doi: 10.1073/pnas.1718148115.

Shapiro, R.S., Chavez, A., Collins, J.J. CRISPR technologies: a toolkit for making genetically intractable microbes tractable. Nature Reviews Microbiology. 2018; doi:10.1038/s41579-018-0002-7

#Shapiro, R.S., #Chavez, A., Porter, C.B.M., Hamblin, M., Kaas, C.S., DiCarlo, J.E., Zeng, G., Xu, X., Revtovich, A.V., Kirienko, N.V., Wang, Y., *Church, G.M., and *Collins, J.J. A CRISPR Cas9-based gene drive platform for genetic interaction analysis in Candida albicans. Nature Microbiology. 2017; doi: 10.1038/s41564-017-0043-0.

Chari, R., Yeo, N.C., Chavez, A., Church, G.M. sgRNA Scorer 2.0: A Species-Independent Model To Predict CRISPR/Cas9 Activity. ACS Synthetic Biology. 2017; 6:902-90: NIHMS: 857197

Rock, J.M., Hopkins, F.F., Chavez, A., Diallo, M., Gerrick, E.R., Prichard, J.R., Church, G.M., Rubin, E.J., Sassetti, C.M., Schnappinger, D., and Fortune, S.M. Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform. Nature Microbiology. 2016; 2:16274: PMCID: PMC5302332

*#Chavez, A., #Pruitt, B.W., Tuttle, M., Shapiro, R.S., Cecchi, R.J., Winston, J., Turczyk, B.M., Tung, M., Collins, J.J., and Church, G.M*. Precise Cas9 targeting enables genomic mutation prevention. bioRxiv. 2016

Nobel, C., Min, J., Olejarz, J., Buchthal, J., Chavez, A., Smidler, A.L., DeBenedictis, E.A., Church, G.M., Nowak, M.A., and Esvelt, K.M. Daisy-chain gene drives for the alteration of local populations. bioRxiv. 2016

#Chavez, A., #Tuttle, M., Pruitt, B.W., Ewen-Campen, B., Chari, R., Ter-Ovanesyan, D., Haque, S.J., Cecchi, R.J., Kowal, E.J., Buchthal, J., Housden, B.E., Perrimon, N., Collins, J.J., and Church, G. Comparison of Cas9 activators in multiple species. Nature Methods. 2016; 13:563-567: PMCID: PMC4927356

#Kiani, S., #Chavez, A., Tuttle, M., Hall, R.N., Chari, R., Ter-Ovanesyan, D., Qian, J., Pruitt, B.W., Beal, J., Vora, S., Buchthal, J., Kowal, E.J., Ebrahimkhani, M.R., Collins, J.J., Weiss, R., Church., G. Cas9 gRNA engineering for genome editing, activation and repression. Nature Methods. 2015; 12:1051-1054: PMCID: PMC4666719

#DiCarlo, J.E., #Chavez, A., Dietz, S.L., Esvelt, K.M., Church, G.M. Safeguarding CRISPR-Cas9 gene drives in yeast. Nature Biotechnology. 2015; 33:1250-1255: PMCID: PMC4675690

#Chavez, A., #Scheiman, J., #Vora, S., Pruitt, B.W., Tuttle, M., P R Iyer, E., Lin, S., Kiani, S., Guzman, C. D., Wiegand, D.J., Ter-Ovanesyan, D., Braff, J.L., Davidsohn, N., Housden, B.E., Perrimon, N., Weiss, R., Aach, J., Collins, J.J., and Church, G.M. Highly efficient Cas9-mediated transcriptional programming. Nature Methods. 2015; 12:326-328: PMCID: PMC4393883

Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., Higgins, J. M., Moltchanov, V., Kuo, F. C., Kluk, M. J., Henderson, B., Kinnunen, L., Koistinen, H. A., Ladenvall, C., Getz, G., Correa, A., Banahan, B. F., Gabriel, S., Kathiresan, S., Stringham, H. M., McCarthy, M. I., Boehnke, M., Tuomilehto, J., Haiman, C., Groop, L., Atzmon, G., Wilson, J. G., Neuberg, D., Altshuler, D., and Ebert, B. L. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 2014; 371:2488–2498: PMCID: PMC4306669

#Glineburg M.R., #Chavez A., Agrawal V., Brill S.J., Johnson F.B. Resolution by unassisted Top3 points to template switch recombination intermediates during DNA replication. J Biol Chem. 2013; 288:33193-33204: PMCID: PMC3829166

Platt, J. M., Ryvkin, P., Wanat, J. J., Donahue, G., Ricketts, M. D., Barrett, S. P., Waters, H. J., Song, S., Chavez, A., Abdallah, K. O., Master, S. R., Wang, L. S., and Johnson, F. B. Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence. Genes & Development. 2013; 27:1406-1420: PMCID: PMC3701195

Chi, A.W-S., Chavez, A., Xu, L., Weber, B.N., Shestova, O., Schaffer, A., Wertheim, G., Pear, W.S., Izon, D., Bhandoola, A. Identification of Flt3+CD150– myeloid progenitors in adult mouse bone marrow that harbor T lymphoid developmental potential. Blood. 2011; 118:2723-2732: PMCID: PMC3172791

Weber, B.N., Chi, A.W., Chavez, A., Yashiro-Ohtani, Y., Yang, Q., Shestova, O., Bhandoola, A. A critical role for TCF-1 in T-lineage specification and differentiation. Nature. 2011; 476:63-68: PMCID: PMC3156435

Chavez, A., Agrawal, V., Johnson, F.B. Homologous recombination-dependent rescue of Smc5/6 deficiency. J Biol Chem.  2011; 286:5119-5125: PMCID: PMC3037623

Chavez, A., George, V., Agrawal, V., Johnson, F.B. Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. J Biol Chem. 2010; 285:11922-11930: PMCID: PMC2852929

Kozak, M.L., Chavez, A., Dang, W., Berger, S.L., Ashok, A., Guo, X., Johnson, F.B. Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction. EMBO J. 2009; 29:158-70: PMCID: PMC2808364

Lee, J.Y., Mogen, J.L., Chavez, A., Johnson F.B. Sgs1 RecQ helicase inhibits survival of Saccharomyces cerevisiae cells lacking telomerase and homologous recombination. J Biol Chem. 2008; 283:29847-29858: PMCID: PMC2573055

Turaga, R.V., Massip, L., Chavez, A., Johnson F.B., Lebel M. Werner and Bloom Syndrome proteins prevent DNA breaks upon chromatin structure alteration. Aging Cell. 2007; 6:471-81

Nollen, E.A., Garcia, S.M., van Haaften, G., Kim, S., Chavez, A., Morimoto, R.I., Plasterk, R.H. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation.  Proc. Natl. Acad. Sci. U. S. A. 2004; 101:6403-6408: PMCID: PMC404057

Up to date publication list:

  • Neural Degeneration and Repair
  • Technology Development 
  • Synthetic Biology 
  • Genomics