Photo of Luca Pinello,  PhD

Luca Pinello, PhD

Massachusetts General Hospital

Massachusetts General Hospital

Luca Pinello, PhD

Massachusetts General Hospital


  • Associate Professor, Pathology, Harvard Medical School
  • Associate Pathologist, Pathology, Massachusetts General Hospital
  • Associate Member, Epigenomics Program, Broad Institute of MIT and Harvard


Research Abstract

I am a computational biologist studying the role of chromatin structure/dynamics and non-coding regions including enhancers, promoters, insulators and their role in gene regulation. The mission of my lab is the integration of omics data to explore and better understand the functional mechanisms of the non-coding genome and to provide accessible tools for the community to accelerate discovery in this field. The long-term goal of my research is to develop innovative computational approaches and to use cutting-edge experimental assays, such as single cell and genome editing, to systematically analyze sources of genetic and epigenetic variation that affect gene regulation in development and in different human traits and diseases.


I have developed several computational strategies to unravel the relationship between epigenetic regulators, chromatin structure and DNA sequence, and how these factors influence gene expression patterns. For example, HAYSTACK ( ) uses histone modification and gene expression data measured across multiple cell-lines to identify the most epigenetically variable regions of the genome to find cell-type specific regulators and to predict cell-type specific chromatin patterns.

Genome Editing

I fully embraced the revolution in functional genomics made possible by the novel genome editing approaches such as CRISPR/Cas9. I have developed computational tools to quantify and visualize the outcome of genome editing experiments, that are nowadays the standard the facto for the community. For example, CRISPResso ( /CRISPResso2 ), an integrated software pipeline for the analysis and visualization of CRISPR/Cas9 outcomes from deep sequencing experiments. This analysis can be used for the assessment of on-target editing efficiency as well as for analysis of off-target editing at selected loci with increased likelihood of off-target mutagenesis. A streamlined and user-friendly website is also available at

Single-cell omics

I am also actively involved in the single-cell community and I am part of the Human Cell Atlas initiative, proposing computational strategies to model gene expression variability, its relationship with chromatin accessibility and DNA methylation, and to reconstruct developmental trajectories. Recently we have developed a method called STREAM (Single-cell Trajectory Reconstruct Exploration and Mapping). This is one of the first methods to perform trajectory inference not only from transcriptomic data but as well epigenomic data such as scATAC-seq ( We have also created an interactive website that can be used interactively to compute trajectories and a reference database of precomputed trajectories for several published studies available at

The full list of software developed in my lab is available at:

Publications from Harvard Catalyst Profiles

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  • Tak YE, Horng JE, Perry NT, Schultz HT, Iyer S, Yao Q, Zou LS, Aryee MJ, Pinello L, Joung JK. Augmenting and directing long-range CRISPR-mediated activation in human cells. Nat Methods 2021. PubMed
  • Yamauchi T, Miyawaki K, Semba Y, Takahashi M, Izumi Y, Nogami J, Nakao F, Sugio T, Sasaki K, Pinello L, Bauer DE, Bamba T, Akashi K, Maeda T. Targeting leukemia-specific dependence on the de novo purine synthesis pathway. Leukemia 2021. PubMed
  • Wang L, Zhang Q, Qin Q, Trasanidis N, Vinyard M, Chen H, Pinello L. Current progress and potential opportunities to infer single-cell developmental trajectory and cell fate. Curr Opin Syst Biol 2021; 26:1-11. PubMed
  • Vinjamur DS, Yao Q, Cole MA, McGuckin C, Ren C, Zeng J, Hossain M, Luk K, Wolfe SA, Pinello L, Bauer DE. ZNF410 represses fetal globin by singular control of CHD4. Nat Genet 2021; 53:719-728. PubMed
  • Petri K, Zhang W, Ma J, Schmidts A, Lee H, Horng JE, Kim DY, Kurt IC, Clement K, Hsu JY, Pinello L, Maus MV, Joung JK, Yeh JJ. CRISPR prime editing with ribonucleoprotein complexes in zebrafish and primary human cells. Nat Biotechnol 2021. PubMed
  • Yao Q, Ferragina P, Reshef Y, Lettre G, Bauer DE, Pinello L. Motif-Raptor: A Cell Type-Specific and Transcription Factor Centric Approach for Post-GWAS Prioritization of Causal Regulators. Bioinformatics 2021. PubMed
  • Rao S, Yao Y, Soares de Brito J, Yao Q, Shen AH, Watkinson RE, Kennedy AL, Coyne S, Ren C, Zeng J, Serbin AV, Studer S, Ballotti K, Harris CE, Luk K, Stevens CS, Armant M, Pinello L, Wolfe SA, Chiarle R, Shimamura A, Lee B, Newburger PE, Bauer DE. Dissecting ELANE neutropenia pathogenicity by human HSC gene editing. Cell Stem Cell 2021. PubMed
  • Hsu JY, Grünewald J, Szalay R, Shih J, Anzalone AV, Lam KC, Shen MW, Petri K, Liu DR, Keith Joung J, Pinello L. PrimeDesign software for rapid and simplified design of prime editing guide RNAs. Nat Commun 2021; 12:1034. PubMed
  • Liu N, Xu S, Yao Q, Zhu Q, Kai Y, Hsu JY, Sakon P, Pinello L, Yuan GC, Bauer DE, Orkin SH. Transcription factor competition at the γ-globin promoters controls hemoglobin switching. Nat Genet 2021; 53:511-520. PubMed
  • Li CM, Shapiro H, Tsiobikas C, Selfors LM, Chen H, Rosenbluth J, Moore K, Gupta KP, Gray GK, Oren Y, Steinbaugh MJ, Guerriero JL, Pinello L, Regev A, Brugge JS. Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing. Cell Rep 2020; 33:108566. PubMed
  • Yao Q, Epstein CB, Banskota S, Issner R, Kim Y, Bernstein BE, Pinello L, Asgari MM. Epigenetic Alterations in Keratinocyte Carcinoma. J Invest Dermatol 2020. PubMed
  • Canver MC, Tripathi P, Bullen MJ, Olshansky M, Kumar Y, Wong LH, Turner SJ, Lessard S, Pinello L, Orkin SH, Das PP. A saturating mutagenesis CRISPR-Cas9 mediated functional genomic screen identifies cis- and trans-regulatory elements of Oct4 in murine ESCs. J Biol Chem 2020. PubMed
  • Clement K, Hsu JY, Canver MC, Joung JK, Pinello L. Technologies and Computational Analysis Strategies for CRISPR Applications. Mol Cell 2020; 79:11-29. PubMed
  • Cancellieri S, Canver MC, Bombieri N, Giugno R, Pinello L. CRISPRitz: rapid, high-throughput and variant-aware in silico off-target site identification for CRISPR genome editing. Bioinformatics 2020; 36:2001-2008. PubMed
  • Albergante L, Mirkes E, Bac J, Chen H, Martin A, Faure L, Barillot E, Pinello L, Gorban A, Zinovyev A. Robust and Scalable Learning of Complex Intrinsic Dataset Geometry via ElPiGraph. Entropy (Basel) 2020. PubMed
  • Kim IS, Wu J, Rahme GJ, Battaglia S, Dixit A, Gaskell E, Chen H, Pinello L, Bernstein BE. Parallel Single-Cell RNA-Seq and Genetic Recording Reveals Lineage Decisions in Developing Embryoid Bodies. Cell Rep 2020; 33:108222. PubMed
  • Ten Hacken E, Clement K, Li S, Hernández-Sánchez M, Redd R, Wang S, Ruff D, Gruber M, Baranowski K, Jacob J, Flynn J, Jones KW, Neuberg D, Livak KJ, Pinello L, Wu CJ. High throughput single-cell detection of multiplex CRISPR-edited gene modifications. Genome Biol 2020; 21:266. PubMed
  • Lähnemann D, Köster J, Szczurek E, McCarthy DJ, Hicks SC, Robinson MD, Vallejos CA, Campbell KR, Beerenwinkel N, Mahfouz A, Pinello L, Skums P, Stamatakis A, Attolini CS, Aparicio S, Baaijens J, Balvert M, Barbanson B, Cappuccio A, Corleone G, Dutilh BE, Florescu M, Guryev V, Holmer R, Jahn K, Lobo TJ, Keizer EM, Khatri I, Kielbasa SM, Korbel JO, Kozlov AM, Kuo TH, Lelieveldt BPF, Mandoiu II, Marioni JC, Marschall T, Mölder F, Niknejad A, Raczkowski L, Reinders M, Ridder J, Saliba AE, Somarakis A, Stegle O, Theis FJ, Yang H, Zelikovsky A, McHardy AC, Raphael BJ, Shah SP, Schönhuth A. Eleven grand challenges in single-cell data science. Genome Biol 2020; 21:31. PubMed
  • Chen H, Lareau C, Andreani T, Vinyard ME, Garcia SP, Clement K, Andrade-Navarro MA, Buenrostro JD, Pinello L. Assessment of computational methods for the analysis of single-cell ATAC-seq data. Genome Biol 2019; 20:241. PubMed
  • Vinyard ME, Su C, Siegenfeld AP, Waterbury AL, Freedy AM, Gosavi PM, Park Y, Kwan EE, Senzer BD, Doench JG, Bauer DE, Pinello L, Liau BB. CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML. Nat Chem Biol 2019; 15:529-539. PubMed
  • Chen H, Albergante L, Hsu JY, Lareau CA, Lo Bosco G, Guan J, Zhou S, Gorban AN, Bauer DE, Aryee MJ, Langenau DM, Zinovyev A, Buenrostro JD, Yuan GC, Pinello L. Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM. Nat Commun 2019; 10:1903. PubMed
  • Clement K, Rees H, Canver MC, Gehrke JM, Farouni R, Hsu JY, Cole MA, Liu DR, Joung JK, Bauer DE, Pinello L. CRISPResso2 provides accurate and rapid genome editing sequence analysis. Nat Biotechnol 2019; 37:224-226. PubMed
  • Hsu JY, Fulco CP, Cole MA, Canver MC, Pellin D, Sher F, Farouni R, Clement K, Guo JA, Biasco L, Orkin SH, Engreitz JM, Lander ES, Joung JK, Bauer DE, Pinello L. CRISPR-SURF: discovering regulatory elements by deconvolution of CRISPR tiling screen data. Nat Methods 2018; 15:992-993. PubMed
  • Canver MC, Bauer DE, Maeda T, Pinello L. DrugThatGene: integrative analysis to streamline the identification of druggable genes, pathways, and protein complexes from CRISPR screens. Bioinformatics 2018. PubMed
  • Canver MC, Haeussler M, Bauer DE, Orkin SH, Sanjana NE, Shalem O, Yuan GC, Zhang F, Concordet JP, Pinello L. Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments. Nat Protoc 2018; 13:946-986. PubMed
  • Pinello L, Farouni R, Yuan GC. Haystack: systematic analysis of the variation of epigenetic states and cell-type specific regulatory elements. Bioinformatics 2018. PubMed
  • Canver MC, Joung JK, Pinello L. Impact of Genetic Variation on CRISPR-Cas Targeting. CRISPR J 2018; 1:159-170. PubMed
  • Schoonenberg VAC, Cole MA, Yao Q, Macias-Treviño C, Sher F, Schupp PG, Canver MC, Maeda T, Pinello L, Bauer DE. CRISPRO: identification of functional protein coding sequences based on genome editing dense mutagenesis. Genome Biol 2018; 19:169. PubMed
  • Clement K, Farouni R, Bauer DE, Pinello L. AmpUMI: design and analysis of unique molecular identifiers for deep amplicon sequencing. Bioinformatics 2018; 34:i202-i210. PubMed
  • Beyaz S, Kim JH, Pinello L, Xifaras ME, Hu Y, Huang J, Kerenyi MA, Das PP, Barnitz RA, Herault A, Dogum R, Haining WN, Yilmaz ÖH, Passegue E, Yuan GC, Orkin SH, Winau F. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol 2017; 18:184-195. PubMed
  • Huang D, Guo G, Yuan P, Ralston A, Sun L, Huss M, Mistri T, Pinello L, Ng HH, Yuan G, Ji J, Rossant J, Robson P, Han X. The role of Cdx2 as a lineage specific transcriptional repressor for pluripotent network during the first developmental cell lineage segregation. Sci Rep 2017; 7:17156. PubMed