Contact Information Childrens Hospital Bldg R S5.224 Office 513-636-6089 Email grimesln@ucmail.uc.edu Research InterestsRecently, I collaborated with Jose Cancelas (CCHMC) and Carolyn Lutzko (CCHMC) to generate iPSC from SCN patients, and to clearly demonstrate the role of mutant-neutrophil elastase in the pathogenesis of SCN. We are currently focused upon dissecting the transcriptional and epigenetic programming engendered by both normal and SCN-mutant Gfi1. To this end we have generated deep single cell RNA Seq (scRNA Seq) data sets from bone marrow stem/progenitor cells, and have collaborated with Nathan Salomonis... Peer Reviewed Publications Dwivedi, Pankaj; Chutipongtanate, Somchai; Muench, David E; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2020. SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling. Proteomics. Clinical applications, , e1900144Hinge, Ashwini; He, Jingyi; Bartram, James; Javier, Jose; Xu, Juying; Fjellman, Ellen; Sesaki, Hiromi; Li, Tingyu; Yu, Jie; Wunderlich, Mark; Mulloy, James; Kofron, Matthew; Salomonis, Nathan; Grimes, H Leighton; Filippi, Marie-Dominique 2020. Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition. Cell stem cell, 26 3, 420-430.e6Lucas, Daniel; Salomonis, Nathan; Grimes, H Leighton 2020. Unraveling bone marrow architecture. Nature cell biology, 22 1, 5-6Yue, Lanzhu; Sharma, Vasundhara; Horvat, Nathan P; Akuffo, Afua A; Beatty, Matthew S; Murdun, Cem; Colin, Christelle; Billington, Julia M R; Goodheart, William E; Sahakian, Eva; Zhang, Ling; Powers, John J; Amin, Narmin E; Lambert-Showers, Que T; Darville, Lancia N; Pinilla-Ibarz, Javier; Reuther, Gary W; Wright, Kenneth L; Conti, Chiara; Lee, Jennifer Y; Zheng, Xiaozhang; Ng, Pui Yee; Martin, Matthew W; Marshall, C Gary; Koomen, John M; Levine, Ross L; Verma, Amit; Grimes, H Leighton; Sotomayor, Eduardo M; Shao, Zonghong; Epling-Burnette, Pearlie K 2020. HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms. Blood, 135 3, 191-207Adelman, Emmalee R; Huang, Hsuan-Ting; Roisman, Alejandro; Olsson, André; Colaprico, Antonio; Qin, Tingting; Lindsley, R Coleman; Bejar, Rafael; Salomonis, Nathan; Grimes, H Leighton; Figueroa, Maria E 2019. Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia. Cancer discovery, 9 8, 1080-1101DePasquale, Erica A K; Schnell, Daniel J; Van Camp, Pieter-Jan; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Singh, Harinder; Salomonis, Nathan 2019. DoubletDecon: Deconvoluting Doublets from Single-Cell RNA-Sequencing Data. Cell reports, 29 6, 1718-1727.e8DePasquale, Erica A K; Schnell, Daniel; Dexheimer, Phillip; Ferchen, Kyle; Hay, Stuart; Chetal, Kashish; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Salomonis, Nathan 2019. cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes. Nucleic acids research, 47 21, e138Duy, Cihangir; Teater, Matt; Garrett-Bakelman, Francine E; Lee, Tak C; Meydan, Cem; Glass, Jacob L; Li, Meng; Hellmuth, Johannes C; Mohammad, Helai P; Smitheman, Kimberly N; Shih, Alan H; Abdel-Wahab, Omar; Tallman, Martin S; Guzman, Monica L; Muench, David; Grimes, H Leighton; Roboz, Gail J; Kruger, Ryan G; Creasy, Caretha L; Paietta, Elisabeth M; Levine, Ross L; Carroll, Martin; Melnick, Ari M 2019. Rational Targeting of Cooperating Layers of the Epigenome Yields Enhanced Therapeutic Efficacy against AML. Cancer discovery, 9 7, 872-889Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2019. Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors. Scientific data, 6 1, 21Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2019. Time resolved quantitative phospho-tyrosine analysis reveals Bruton's Tyrosine kinase mediated signaling downstream of the mutated granulocyte-colony stimulating factor receptors. Leukemia, 33 1, 75-87Lee, Catherine; Rudneva, Vasilisa A; Erkek, Serap; Zapatka, Marc; Chau, Lianne Q; Tacheva-Grigorova, Silvia K; Garancher, Alexandra; Rusert, Jessica M; Aksoy, Ozlem; Lea, Robin; Mohammad, Helai P; Wang, Jianxun; Weiss, William A; Grimes, H Leighton; Pfister, Stefan M; Northcott, Paul A; Wechsler-Reya, Robert J 2019. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma. Nature communications, 10 1, 332Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Virendra K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton 2019. Author Correction: Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature, 569 7755, E3Park, Derek S; Akuffo, Afua A; Muench, David E; Grimes, H Leighton; Epling-Burnette, Pearlie K; Maini, Philip K; Anderson, Alexander R A; Bonsall, Michael B 2019. Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation. PLoS computational biology, 15 4, e1006913Hay, Stuart B; Ferchen, Kyle; Chetal, Kashish; Grimes, H Leighton; Salomonis, Nathan 2018. The Human Cell Atlas bone marrow single-cell interactive web portal. Experimental hematology, 68 , 51-61Hayashi, Yoshihiro; Zhang, Yue; Yokota, Asumi; Yan, Xiaomei; Liu, Jinqin; Choi, Kwangmin; Li, Bing; Sashida, Goro; Peng, Yanyan; Xu, Zefeng; Huang, Rui; Zhang, Lulu; Freudiger, George M; Wang, Jingya; Dong, Yunzhu; Zhou, Yile; Wang, Jieyu; Wu, Lingyun; Bu, Jiachen; Chen, Aili; Zhao, Xinghui; Sun, Xiujuan; Chetal, Kashish; Olsson, Andre; Watanabe, Miki; Romick-Rosendale, Lindsey E; Harada, Hironori; Shih, Lee-Yung; Tse, William; Bridges, James P; Caligiuri, Michael A; Huang, Taosheng; Zheng, Yi; Witte, David P; Wang, Qian-Fei; Qu, Cheng-Kui; Salomonis, Nathan; Grimes, H Leighton; Nimer, Stephen D; Xiao, Zhijian; Huang, Gang 2018. Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes. Cancer discovery, 8 11, 1438-1457Kleeman, Benjamin; Olsson, Andre; Newkold, Tess; Kofron, Matt; DeLay, Monica; Hildeman, David; Grimes, H Leighton 2018. A guide to choosing fluorescent protein combinations for flow cytometric analysis based on spectral overlap. Cytometry. Part A : the journal of the International Society for Analytical Cytology, 93 5, 556-562Lee, Jung-Mi; Govindarajah, Vinothini; Goddard, Bryan; Hinge, Ashwini; Muench, David E; Filippi, Marie-Dominique; Aronow, Bruce; Cancelas, Jose A; Salomonis, Nathan; Grimes, H Leighton; Reynaud, Damien 2018. Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression. The Journal of experimental medicine, 215 2, 627-644Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S 2018. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell reports, 25 11, 3229Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S 2018. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell reports, 25 8, 2083-2093.e4Meyer, Sara E; Muench, David E; Rogers, Andrew M; Newkold, Tess J; Orr, Emily; O'Brien, Eric; Perentesis, John P; Doench, John G; Lal, Ashish; Morris, Patrick J; Thomas, Craig J; Lieberman, Judy; McGlinn, Edwina; Aronow, Bruce J; Salomonis, Nathan; Grimes, H Leighton 2018. miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential. The Journal of experimental medicine, 215 8, 2115-2136Muench, David E; Ferchen, Kyle; Velu, Chinavenmeni S; Pradhan, Kith; Chetal, Kashish; Chen, Xiaoting; Weirauch, Matthew T; Colmenares, Clemencia; Verma, Amit; Salomonis, Nathan; Grimes, H Leighton 2018. SKI controls MDS-associated chronic TGF-? signaling, aberrant splicing, and stem cell fitness. Blood, 132 21, e24-e34Zhang, Cuiping; D'Alessandro, Angelo; Wellendorf, Ashley M; Mohmoud, Fatima; Serrano-Lopez, Juana; Perentesis, John P; Komurov, Kakajan; Alexe, Gabriela; Stegmaier, Kimberly; Whitsett, Jeffrey A; Grimes, H Leighton; Cancelas, Jose A 2018. KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia. Oncotarget, 9 51, 29665-29679Zhou, Yile; Yan, Xiaomei; Feng, Xiaomin; Bu, Jiachen; Dong, Yunzhu; Lin, Peipei; Hayashi, Yoshihiro; Huang, Rui; Olsson, Andre; Andreassen, Paul R; Grimes, H Leighton; Wang, Qian-Fei; Cheng, Tao; Xiao, Zhijian; Jin, Jie; Huang, Gang 2018. Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation. Haematologica, 103 7, 1110-1123Kesarwani, Meenu; Kincaid, Zachary; Gomaa, Ahmed; Huber, Erika; Rohrabaugh, Sara; Siddiqui, Zain; Bouso, Muhammad F; Latif, Tahir; Xu, Ming; Komurov, Kakajan; Mulloy, James C; Cancelas, Jose A; Grimes, H Leighton; Azam, Mohammad 2017. Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nature medicine, 23 4, 472-482Yáñez, Alberto; Coetzee, Simon G; Olsson, Andre; Muench, David E; Berman, Benjamin P; Hazelett, Dennis J; Salomonis, Nathan; Grimes, H Leighton; Goodridge, Helen S 2017. Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes. Immunity, 47 5, 890-902.e4Yáñez, Alberto; Goodridge, Helen S; Grimes, H Leighton 2017. Counting the cost of lineage decisions. Nature immunology, 18 8, 872-873Meyer, Sara E; Qin, Tingting; Muench, David E; Masuda, Kohei; Venkatasubramanian, Meenakshi; Orr, Emily; Suarez, Lauren; Gore, Steven D; Delwel, Ruud; Paietta, Elisabeth; Tallman, Martin S; Fernandez, Hugo; Melnick, Ari; Le Beau, Michelle M; Kogan, Scott; Salomonis, Nathan; Figueroa, Maria E; Grimes, H Leighton 2016. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer discovery, 6 5, 501-15Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Viren K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton 2016. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature, 537 7622, 698-702Muench, David E; Grimes, H Leighton 2015. Transcriptional Control of Stem and Progenitor Potential. Current stem cell reports, 1 3, 139-150Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A 2015. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. The Journal of clinical investigation, 125 8, 3103-16Boespflug, Nicholas D; Kumar, Sachin; McAlees, Jaclyn W; Phelan, James D; Grimes, H Leighton; Hoebe, Kasper; Hai, Tsonwin; Filippi, Marie-Dominique; Karp, Christopher L 2014. ATF3 is a novel regulator of mouse neutrophil migration. Blood, 123 13, 2084-93Fang, Jing; Barker, Brenden; Bolanos, Lyndsey; Liu, Xiaona; Jerez, Andres; Makishima, Hideki; Christie, Susanne; Chen, Xiaoting; Rao, Dinesh S; Grimes, H Leighton; Komurov, Kakajan; Weirauch, Matthew T; Cancelas, Jose A; Maciejewski, Jaroslaw P; Starczynowski, Daniel T 2014. Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-?B gene network. Cell reports, 8 5, 1328-38Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M 2014. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature, 511 7510, 428-34Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C; Trump, Lisa; Salipante, Stephen J; Cheng, Jerry C; Donadieu, Jean; Glaubach, Taly; Corey, Seth J; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A; Horwitz, Marshall S 2014. Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms. Blood, 123 4, 562-9Velu, Chinavenmeni S; Chaubey, Aditya; Phelan, James D; Horman, Shane R; Wunderlich, Mark; Guzman, Monica L; Jegga, Anil G; Zeleznik-Le, Nancy J; Chen, Jianjun; Mulloy, James C; Cancelas, Jose A; Jordan, Craig T; Aronow, Bruce J; Marcucci, Guido; Bhat, Balkrishen; Gebelein, Brian; Grimes, H Leighton 2014. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. The Journal of clinical investigation, 124 1, 222-36Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A; Mizukawa, Benjamin; Grimes, H Leighton; Kurokawa, Mineo; Liu, P Paul; Huang, Gang; Mulloy, James C 2013. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. The Journal of clinical investigation, 123 9, 3876-88Horwitz, Marshall S; Corey, Seth J; Grimes, H Leighton; Tidwell, Timothy 2013. ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematology/oncology clinics of North America, 27 1, 19-41, viiKhandanpour, Cyrus; Phelan, James D; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H Leighton; Möröy, Tarik 2013. Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer cell, 23 2, 200-14Phelan, James D; Saba, Ingrid; Zeng, Hui; Kosan, Christian; Messer, Malynda S; Olsson, H Andre; Fraszczak, Jennifer; Hildeman, David A; Aronow, Bruce J; Möröy, Tarik; Grimes, H Leighton 2013. Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS genetics, 9 9, e1003713Raines, Anna M; Adam, Mike; Magella, Bliss; Meyer, Sara E; Grimes, H Leighton; Dey, Sudhansu K; Potter, S Steven 2013. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development (Cambridge, England), 140 14, 2942-52Khandanpour, Cyrus; Krongold, Joseph; Schütte, Judith; Bouwman, Frederique; Vassen, Lothar; Gaudreau, Marie-Claude; Chen, Riyan; Calero-Nieto, Fernando J; Diamanti, Evangelia; Hannah, Rebecca; Meyer, Sara E; Grimes, H Leighton; van der Reijden, Bert A; Jansen, Joop H; Patel, Chandrashekhar V; Peeters, Justine K; Löwenberg, Bob; Dührsen, Ulrich; Göttgens, Bertie; Möröy, Tarik 2012. The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice. Blood, 120 19, 4006-17Stoffers, Sara L; Meyer, Sara E; Grimes, H Leighton 2012. MicroRNAs in the midst of myeloid signal transduction. Journal of cellular physiology, 227 2, 525-33Unnisa, Zeenath; Clark, Jason P; Roychoudhury, Jayeeta; Thomas, Elizabeth; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Grimes, H Leighton; Kumar, Ashish R 2012. Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress. Blood, 120 25, 4973-81Velu, Chinavenmeni S; Grimes, H Leighton 2012. Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone marrow cells. Methods in molecular biology (Clifton, N.J.), 928 , 185-95Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M; Witte, David; Wang, Qian-Fei; Tenen, Daniel G; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C; Grimes, H Leighton; Caligiuri, Michael A; Huang, Gang 2012. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood, 120 5, 1118-29D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L; Patrene, Kenneth D; Yu, Shibing; Velu, Chinavenmeni S; Xiao, Guozhi; Grimes, H Leighton; Roodman, G David; Galson, Deborah L 2011. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease. Blood, 118 26, 6871-80Guo, Fukun; Zhang, Shuangmin; Tripathi, Pulak; Mattner, Jochen; Phelan, James; Sproles, Alyssa; Mo, Jun; Wills-Karp, Marsha; Grimes, H Leighton; Hildeman, David; Zheng, Yi 2011. Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation. PloS one, 6 3, e18002Kurtulus, Sema; Tripathi, Pulak; Moreno-Fernandez, Maria E; Sholl, Allyson; Katz, Jonathan D; Grimes, H Leighton; Hildeman, David A 2011. Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim. Journal of immunology (Baltimore, Md. : 1950), 186 10, 5729-37McClendon, A Kathleen; Dean, Jeffry L; Ertel, Adam; Fu, Zhiyan; Rivadeneira, Dayana B; Reed, Christopher A; Bourgo, Ryan J; Witkiewicz, Agnieszka; Addya, Sankar; Mayhew, Christopher N; Grimes, H Leighton; Fortina, Paolo; Knudsen, Erik S 2011. RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage. Gastroenterology, 141 4, 1439-50Barnes, Michael J; Aksoylar, Halil; Krebs, Philippe; Bourdeau, Tristan; Arnold, Carrie N; Xia, Yu; Khovananth, Kevin; Engel, Isaac; Sovath, Sosathya; Lampe, Kristin; Laws, Eleana; Saunders, Amy; Butcher, Geoffrey W; Kronenberg, Mitchell; Steinbrecher, Kris; Hildeman, David; Grimes, H Leighton; Beutler, Bruce; Hoebe, Kasper 2010. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice. Journal of immunology (Baltimore, Md. : 1950), 184 7, 3743-54Guo, Fukun; Hildeman, David; Tripathi, Pulak; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi 2010. Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 107 43, 18505-10Kong, Kimi Y; Owens, Kristin S; Rogers, Jason H; Mullenix, Jason; Velu, Chinavenmeni S; Grimes, H Leighton; Dahl, Richard 2010. MIR-23A microRNA cluster inhibits B-cell development. Experimental hematology, 38 8, 629-640.e1Meyer, Sara E; Hasenstein, Jason R; Baktula, Avinash; Velu, Chinavenmani S; Xu, Yan; Wan, Huajing; Whitsett, Jeffrey A; Gilks, C Blake; Grimes, H Leighton 2010. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. The American journal of pathology, 177 3, 1503-13Phelan, James D; Shroyer, Noah F; Cook, Tiffany; Gebelein, Brian; Grimes, H Leighton 2010. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Current opinion in hematology, 17 4, 300-7Sharif-Askari, Ehssan; Vassen, Lothar; Kosan, Christian; Khandanpour, Cyrus; Gaudreau, Marie-Claude; Heyd, Florian; Okayama, Taro; Jin, Jianmin; Rojas, Meghan E B; Grimes, H Leighton; Zeng, Hui; Möröy, Tarik 2010. Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65. Molecular and cellular biology, 30 16, 3929-42Tripathi, Pulak; Kurtulus, Sema; Wojciechowski, Sara; Sholl, Allyson; Hoebe, Kasper; Morris, Suzanne C; Finkelman, Fred D; Grimes, H Leighton; Hildeman, David A 2010. STAT5 is critical to maintain effector CD8+ T cell responses. Journal of immunology (Baltimore, Md. : 1950), 185 4, 2116-24Arumugam, Paritha I; Urbinati, Fabrizia; Velu, Chinavenmeni S; Higashimoto, Tomoyasu; Grimes, H Leighton; Malik, Punam 2009. The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity. PloS one, 4 9, e6995Gu, YuanYuan; Harley, Isaac T W; Henderson, Lindsay B; Aronow, Bruce J; Vietor, Ilja; Huber, Lukas A; Harley, John B; Kilpatrick, Jeffrey R; Langefeld, Carl D; Williams, Adrienne H; Jegga, Anil G; Chen, Jing; Wills-Karp, Marsha; Arshad, S Hasan; Ewart, Susan L; Thio, Chloe L; Flick, Leah M; Filippi, Marie-Dominique; Grimes, H Leighton; Drumm, Mitchell L; Cutting, Garry R; Knowles, Michael R; Karp, Christopher L 2009. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature, 458 7241, 1039-42Guo, Fukun; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi 2009. Rho GTPase Cdc42 is essential for B-lymphocyte development and activation. Blood, 114 14, 2909-16Horman, Shane R; Velu, Chinavenmeni S; Chaubey, Aditya; Bourdeau, Tristan; Zhu, Jinfang; Paul, William E; Gebelein, Brian; Grimes, H Leighton 2009. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood, 113 22, 5466-75Popovic, Relja; Riesbeck, Laurie E; Velu, Chinavenmeni S; Chaubey, Aditya; Zhang, Jiwang; Achille, Nicholas J; Erfurth, Frank E; Eaton, Katherine; Lu, Jun; Grimes, H Leighton; Chen, Jianjun; Rowley, Janet D; Zeleznik-Le, Nancy J 2009. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood, 113 14, 3314-22Salipante, Stephen J; Rojas, Meghan E B; Korkmaz, Brice; Duan, Zhijun; Wechsler, Jeremy; Benson, Kathleen F; Person, Richard E; Grimes, H Leighton; Horwitz, Marshall S 2009. Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase. Molecular and cellular biology, 29 16, 4394-405Velu, Chinavenmeni S; Baktula, Avinash M; Grimes, H Leighton 2009. Gfi1 regulates miR-21 and miR-196b to control myelopoiesis. Blood, 113 19, 4720-8Li-Kroeger, David; Witt, Lorraine M; Grimes, H Leighton; Cook, Tiffany A; Gebelein, Brian 2008. Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Developmental cell, 15 2, 298-308Montoya-Durango, Diego E; Velu, Chinavenmeni S; Kazanjian, Avedis; Rojas, Meghan E B; Jay, Chris M; Longmore, Gregory D; Grimes, H Leighton 2008. Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor. The Journal of biological chemistry, 283 46, 32056-65Zarebski, Adrian; Velu, Chinavenmeni S; Baktula, Avinash M; Bourdeau, Tristan; Horman, Shane R; Basu, Sudeep; Bertolone, Salvatore J; Horwitz, Marshal; Hildeman, David A; Trent, John O; Grimes, H Leighton 2008. Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1. Immunity, 28 3, 370-80Duan, Zhijun; Person, Richard E; Lee, Hu-Hui; Huang, Shi; Donadieu, Jean; Badolato, Raffaele; Grimes, H Leighton; Papayannopoulou, Thalia; Horwitz, Marshall S 2007. Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5. Molecular and cellular biology, 27 19, 6889-902Linnoila, R Ilona; Jensen-Taubman, Sandra; Kazanjian, Avedis; Grimes, H Leighton 2007. Loss of GFI1 impairs pulmonary neuroendorine cell proliferation, but the neuroendocrine phenotype has limited impact on post-naphthalene airway repair. Laboratory investigation; a journal of technical methods and pathology, 87 4, 336-44Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H Leighton; Katz, Jonathan D; Finkelman, Fred D; Hildeman, David A 2007. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. The Journal of experimental medicine, 204 7, 1665-75Kazanjian, Avedis; Gross, Eleanore A; Grimes, H Leighton 2006. The growth factor independence-1 transcription factor: new functions and new insights. Critical reviews in oncology/hematology, 59 2, 85-97Duan, Zhijun; Zarebski, Adrian; Montoya-Durango, Diego; Grimes, H Leighton; Horwitz, Marshall 2005. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Molecular and cellular biology, 25 23, 10338-51Dwivedi, Prem P; Anderson, Paul H; Omdahl, John L; Grimes, H Leighton; Morris, Howard A; May, Brian K 2005. Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells. Endocrine-related cancer, 12 2, 351-65Doan, Loretta L; Porter, Susan D; Duan, Zhijun; Flubacher, Marcella M; Montoya, Diego; Tsichlis, Philip N; Horwitz, Marshall; Gilks, C Blake; Grimes, H Leighton 2004. Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic acids research, 32 8, 2508-19Grimes, H Leighton; Schanie, Carrie L; Huang, Yiming; Cramer, Daniel; Rezzoug, Francine; Fugier-Vivier, Isabelle; Ildstad, Suzanne T 2004. Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes. Experimental hematology, 32 10, 946-54Huang, Yiming; Rezzoug, Francine; Chilton, Paula M; Grimes, H Leighton; Cramer, Daniel E; Ildstad, Suzanne T 2004. Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment. Blood, 104 3, 873-80Kazanjian, Avedis; Wallis, Deeann; Au, Nicholas; Nigam, Rupesh; Venken, Koen J T; Cagle, Philip T; Dickey, Burton F; Bellen, Hugo J; Gilks, C Blake; Grimes, H Leighton 2004. Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells. Cancer research, 64 19, 6874-82Park, Jung-Hyun; Yu, Qing; Erman, Batu; Appelbaum, Jacob S; Montoya-Durango, Diego; Grimes, H Leighton; Singer, Alfred 2004. Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity, 21 2, 289-302Doan, Loretta L; Kitay, Mary Kate; Yu, Qing; Singer, Alfred; Herblot, Sabine; Hoang, Trang; Bear, Susan E; Morse, Herbert C; Tsichlis, Philip N; Grimes, H Leighton 2003. Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment. Journal of immunology (Baltimore, Md. : 1950), 170 5, 2356-66Doan, Loretta L; Tanner, Michael K; Grimes, H Leighton 2003. Intranuclear staining of proteins in heterogeneous cell populations and verification of nuclear localization by flow cytometric analysis. Journal of immunological methods, 279 1-2, 193-8McGhee, Laura; Bryan, Josh; Elliott, Liza; Grimes, H Leighton; Kazanjian, Avedis; Davis, J Nathan; Meyers, Shari 2003. Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism. Journal of cellular biochemistry, 89 5, 1005-18Person, Richard E; Li, Feng-Qian; Duan, Zhijun; Benson, Kathleen F; Wechsler, Jeremy; Papadaki, Helen A; Eliopoulos, George; Kaufman, Christina; Bertolone, Salvatore J; Nakamoto, Betty; Papayannopoulou, Thalia; Grimes, H Leighton; Horwitz, Marshall 2003. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nature genetics, 34 3, 308-12Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T; Schumacher, Armin; Grimes, H Leighton; Zoghbi, Huda Y; Orkin, Stuart H; Bellen, Hugo J 2003. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development (Cambridge, England), 130 1, 221-32
Research InterestsRecently, I collaborated with Jose Cancelas (CCHMC) and Carolyn Lutzko (CCHMC) to generate iPSC from SCN patients, and to clearly demonstrate the role of mutant-neutrophil elastase in the pathogenesis of SCN. We are currently focused upon dissecting the transcriptional and epigenetic programming engendered by both normal and SCN-mutant Gfi1. To this end we have generated deep single cell RNA Seq (scRNA Seq) data sets from bone marrow stem/progenitor cells, and have collaborated with Nathan Salomonis...
Peer Reviewed Publications Dwivedi, Pankaj; Chutipongtanate, Somchai; Muench, David E; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2020. SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling. Proteomics. Clinical applications, , e1900144Hinge, Ashwini; He, Jingyi; Bartram, James; Javier, Jose; Xu, Juying; Fjellman, Ellen; Sesaki, Hiromi; Li, Tingyu; Yu, Jie; Wunderlich, Mark; Mulloy, James; Kofron, Matthew; Salomonis, Nathan; Grimes, H Leighton; Filippi, Marie-Dominique 2020. Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition. Cell stem cell, 26 3, 420-430.e6Lucas, Daniel; Salomonis, Nathan; Grimes, H Leighton 2020. Unraveling bone marrow architecture. Nature cell biology, 22 1, 5-6Yue, Lanzhu; Sharma, Vasundhara; Horvat, Nathan P; Akuffo, Afua A; Beatty, Matthew S; Murdun, Cem; Colin, Christelle; Billington, Julia M R; Goodheart, William E; Sahakian, Eva; Zhang, Ling; Powers, John J; Amin, Narmin E; Lambert-Showers, Que T; Darville, Lancia N; Pinilla-Ibarz, Javier; Reuther, Gary W; Wright, Kenneth L; Conti, Chiara; Lee, Jennifer Y; Zheng, Xiaozhang; Ng, Pui Yee; Martin, Matthew W; Marshall, C Gary; Koomen, John M; Levine, Ross L; Verma, Amit; Grimes, H Leighton; Sotomayor, Eduardo M; Shao, Zonghong; Epling-Burnette, Pearlie K 2020. HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms. Blood, 135 3, 191-207Adelman, Emmalee R; Huang, Hsuan-Ting; Roisman, Alejandro; Olsson, André; Colaprico, Antonio; Qin, Tingting; Lindsley, R Coleman; Bejar, Rafael; Salomonis, Nathan; Grimes, H Leighton; Figueroa, Maria E 2019. Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia. Cancer discovery, 9 8, 1080-1101DePasquale, Erica A K; Schnell, Daniel J; Van Camp, Pieter-Jan; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Singh, Harinder; Salomonis, Nathan 2019. DoubletDecon: Deconvoluting Doublets from Single-Cell RNA-Sequencing Data. Cell reports, 29 6, 1718-1727.e8DePasquale, Erica A K; Schnell, Daniel; Dexheimer, Phillip; Ferchen, Kyle; Hay, Stuart; Chetal, Kashish; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Salomonis, Nathan 2019. cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes. Nucleic acids research, 47 21, e138Duy, Cihangir; Teater, Matt; Garrett-Bakelman, Francine E; Lee, Tak C; Meydan, Cem; Glass, Jacob L; Li, Meng; Hellmuth, Johannes C; Mohammad, Helai P; Smitheman, Kimberly N; Shih, Alan H; Abdel-Wahab, Omar; Tallman, Martin S; Guzman, Monica L; Muench, David; Grimes, H Leighton; Roboz, Gail J; Kruger, Ryan G; Creasy, Caretha L; Paietta, Elisabeth M; Levine, Ross L; Carroll, Martin; Melnick, Ari M 2019. Rational Targeting of Cooperating Layers of the Epigenome Yields Enhanced Therapeutic Efficacy against AML. Cancer discovery, 9 7, 872-889Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2019. Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors. Scientific data, 6 1, 21Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D 2019. Time resolved quantitative phospho-tyrosine analysis reveals Bruton's Tyrosine kinase mediated signaling downstream of the mutated granulocyte-colony stimulating factor receptors. Leukemia, 33 1, 75-87Lee, Catherine; Rudneva, Vasilisa A; Erkek, Serap; Zapatka, Marc; Chau, Lianne Q; Tacheva-Grigorova, Silvia K; Garancher, Alexandra; Rusert, Jessica M; Aksoy, Ozlem; Lea, Robin; Mohammad, Helai P; Wang, Jianxun; Weiss, William A; Grimes, H Leighton; Pfister, Stefan M; Northcott, Paul A; Wechsler-Reya, Robert J 2019. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma. Nature communications, 10 1, 332Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Virendra K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton 2019. Author Correction: Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature, 569 7755, E3Park, Derek S; Akuffo, Afua A; Muench, David E; Grimes, H Leighton; Epling-Burnette, Pearlie K; Maini, Philip K; Anderson, Alexander R A; Bonsall, Michael B 2019. Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation. PLoS computational biology, 15 4, e1006913Hay, Stuart B; Ferchen, Kyle; Chetal, Kashish; Grimes, H Leighton; Salomonis, Nathan 2018. The Human Cell Atlas bone marrow single-cell interactive web portal. Experimental hematology, 68 , 51-61Hayashi, Yoshihiro; Zhang, Yue; Yokota, Asumi; Yan, Xiaomei; Liu, Jinqin; Choi, Kwangmin; Li, Bing; Sashida, Goro; Peng, Yanyan; Xu, Zefeng; Huang, Rui; Zhang, Lulu; Freudiger, George M; Wang, Jingya; Dong, Yunzhu; Zhou, Yile; Wang, Jieyu; Wu, Lingyun; Bu, Jiachen; Chen, Aili; Zhao, Xinghui; Sun, Xiujuan; Chetal, Kashish; Olsson, Andre; Watanabe, Miki; Romick-Rosendale, Lindsey E; Harada, Hironori; Shih, Lee-Yung; Tse, William; Bridges, James P; Caligiuri, Michael A; Huang, Taosheng; Zheng, Yi; Witte, David P; Wang, Qian-Fei; Qu, Cheng-Kui; Salomonis, Nathan; Grimes, H Leighton; Nimer, Stephen D; Xiao, Zhijian; Huang, Gang 2018. Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes. Cancer discovery, 8 11, 1438-1457Kleeman, Benjamin; Olsson, Andre; Newkold, Tess; Kofron, Matt; DeLay, Monica; Hildeman, David; Grimes, H Leighton 2018. A guide to choosing fluorescent protein combinations for flow cytometric analysis based on spectral overlap. Cytometry. Part A : the journal of the International Society for Analytical Cytology, 93 5, 556-562Lee, Jung-Mi; Govindarajah, Vinothini; Goddard, Bryan; Hinge, Ashwini; Muench, David E; Filippi, Marie-Dominique; Aronow, Bruce; Cancelas, Jose A; Salomonis, Nathan; Grimes, H Leighton; Reynaud, Damien 2018. Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression. The Journal of experimental medicine, 215 2, 627-644Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S 2018. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell reports, 25 11, 3229Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S 2018. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell reports, 25 8, 2083-2093.e4Meyer, Sara E; Muench, David E; Rogers, Andrew M; Newkold, Tess J; Orr, Emily; O'Brien, Eric; Perentesis, John P; Doench, John G; Lal, Ashish; Morris, Patrick J; Thomas, Craig J; Lieberman, Judy; McGlinn, Edwina; Aronow, Bruce J; Salomonis, Nathan; Grimes, H Leighton 2018. miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential. The Journal of experimental medicine, 215 8, 2115-2136Muench, David E; Ferchen, Kyle; Velu, Chinavenmeni S; Pradhan, Kith; Chetal, Kashish; Chen, Xiaoting; Weirauch, Matthew T; Colmenares, Clemencia; Verma, Amit; Salomonis, Nathan; Grimes, H Leighton 2018. SKI controls MDS-associated chronic TGF-? signaling, aberrant splicing, and stem cell fitness. Blood, 132 21, e24-e34Zhang, Cuiping; D'Alessandro, Angelo; Wellendorf, Ashley M; Mohmoud, Fatima; Serrano-Lopez, Juana; Perentesis, John P; Komurov, Kakajan; Alexe, Gabriela; Stegmaier, Kimberly; Whitsett, Jeffrey A; Grimes, H Leighton; Cancelas, Jose A 2018. KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia. Oncotarget, 9 51, 29665-29679Zhou, Yile; Yan, Xiaomei; Feng, Xiaomin; Bu, Jiachen; Dong, Yunzhu; Lin, Peipei; Hayashi, Yoshihiro; Huang, Rui; Olsson, Andre; Andreassen, Paul R; Grimes, H Leighton; Wang, Qian-Fei; Cheng, Tao; Xiao, Zhijian; Jin, Jie; Huang, Gang 2018. Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation. Haematologica, 103 7, 1110-1123Kesarwani, Meenu; Kincaid, Zachary; Gomaa, Ahmed; Huber, Erika; Rohrabaugh, Sara; Siddiqui, Zain; Bouso, Muhammad F; Latif, Tahir; Xu, Ming; Komurov, Kakajan; Mulloy, James C; Cancelas, Jose A; Grimes, H Leighton; Azam, Mohammad 2017. Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nature medicine, 23 4, 472-482Yáñez, Alberto; Coetzee, Simon G; Olsson, Andre; Muench, David E; Berman, Benjamin P; Hazelett, Dennis J; Salomonis, Nathan; Grimes, H Leighton; Goodridge, Helen S 2017. Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes. Immunity, 47 5, 890-902.e4Yáñez, Alberto; Goodridge, Helen S; Grimes, H Leighton 2017. Counting the cost of lineage decisions. Nature immunology, 18 8, 872-873Meyer, Sara E; Qin, Tingting; Muench, David E; Masuda, Kohei; Venkatasubramanian, Meenakshi; Orr, Emily; Suarez, Lauren; Gore, Steven D; Delwel, Ruud; Paietta, Elisabeth; Tallman, Martin S; Fernandez, Hugo; Melnick, Ari; Le Beau, Michelle M; Kogan, Scott; Salomonis, Nathan; Figueroa, Maria E; Grimes, H Leighton 2016. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer discovery, 6 5, 501-15Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Viren K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton 2016. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature, 537 7622, 698-702Muench, David E; Grimes, H Leighton 2015. Transcriptional Control of Stem and Progenitor Potential. Current stem cell reports, 1 3, 139-150Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A 2015. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. The Journal of clinical investigation, 125 8, 3103-16Boespflug, Nicholas D; Kumar, Sachin; McAlees, Jaclyn W; Phelan, James D; Grimes, H Leighton; Hoebe, Kasper; Hai, Tsonwin; Filippi, Marie-Dominique; Karp, Christopher L 2014. ATF3 is a novel regulator of mouse neutrophil migration. Blood, 123 13, 2084-93Fang, Jing; Barker, Brenden; Bolanos, Lyndsey; Liu, Xiaona; Jerez, Andres; Makishima, Hideki; Christie, Susanne; Chen, Xiaoting; Rao, Dinesh S; Grimes, H Leighton; Komurov, Kakajan; Weirauch, Matthew T; Cancelas, Jose A; Maciejewski, Jaroslaw P; Starczynowski, Daniel T 2014. Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-?B gene network. Cell reports, 8 5, 1328-38Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M 2014. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature, 511 7510, 428-34Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C; Trump, Lisa; Salipante, Stephen J; Cheng, Jerry C; Donadieu, Jean; Glaubach, Taly; Corey, Seth J; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A; Horwitz, Marshall S 2014. Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms. Blood, 123 4, 562-9Velu, Chinavenmeni S; Chaubey, Aditya; Phelan, James D; Horman, Shane R; Wunderlich, Mark; Guzman, Monica L; Jegga, Anil G; Zeleznik-Le, Nancy J; Chen, Jianjun; Mulloy, James C; Cancelas, Jose A; Jordan, Craig T; Aronow, Bruce J; Marcucci, Guido; Bhat, Balkrishen; Gebelein, Brian; Grimes, H Leighton 2014. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. The Journal of clinical investigation, 124 1, 222-36Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A; Mizukawa, Benjamin; Grimes, H Leighton; Kurokawa, Mineo; Liu, P Paul; Huang, Gang; Mulloy, James C 2013. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. The Journal of clinical investigation, 123 9, 3876-88Horwitz, Marshall S; Corey, Seth J; Grimes, H Leighton; Tidwell, Timothy 2013. ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematology/oncology clinics of North America, 27 1, 19-41, viiKhandanpour, Cyrus; Phelan, James D; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H Leighton; Möröy, Tarik 2013. Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer cell, 23 2, 200-14Phelan, James D; Saba, Ingrid; Zeng, Hui; Kosan, Christian; Messer, Malynda S; Olsson, H Andre; Fraszczak, Jennifer; Hildeman, David A; Aronow, Bruce J; Möröy, Tarik; Grimes, H Leighton 2013. Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS genetics, 9 9, e1003713Raines, Anna M; Adam, Mike; Magella, Bliss; Meyer, Sara E; Grimes, H Leighton; Dey, Sudhansu K; Potter, S Steven 2013. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development (Cambridge, England), 140 14, 2942-52Khandanpour, Cyrus; Krongold, Joseph; Schütte, Judith; Bouwman, Frederique; Vassen, Lothar; Gaudreau, Marie-Claude; Chen, Riyan; Calero-Nieto, Fernando J; Diamanti, Evangelia; Hannah, Rebecca; Meyer, Sara E; Grimes, H Leighton; van der Reijden, Bert A; Jansen, Joop H; Patel, Chandrashekhar V; Peeters, Justine K; Löwenberg, Bob; Dührsen, Ulrich; Göttgens, Bertie; Möröy, Tarik 2012. The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice. Blood, 120 19, 4006-17Stoffers, Sara L; Meyer, Sara E; Grimes, H Leighton 2012. MicroRNAs in the midst of myeloid signal transduction. Journal of cellular physiology, 227 2, 525-33Unnisa, Zeenath; Clark, Jason P; Roychoudhury, Jayeeta; Thomas, Elizabeth; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Grimes, H Leighton; Kumar, Ashish R 2012. Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress. Blood, 120 25, 4973-81Velu, Chinavenmeni S; Grimes, H Leighton 2012. Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone marrow cells. Methods in molecular biology (Clifton, N.J.), 928 , 185-95Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M; Witte, David; Wang, Qian-Fei; Tenen, Daniel G; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C; Grimes, H Leighton; Caligiuri, Michael A; Huang, Gang 2012. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood, 120 5, 1118-29D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L; Patrene, Kenneth D; Yu, Shibing; Velu, Chinavenmeni S; Xiao, Guozhi; Grimes, H Leighton; Roodman, G David; Galson, Deborah L 2011. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease. Blood, 118 26, 6871-80Guo, Fukun; Zhang, Shuangmin; Tripathi, Pulak; Mattner, Jochen; Phelan, James; Sproles, Alyssa; Mo, Jun; Wills-Karp, Marsha; Grimes, H Leighton; Hildeman, David; Zheng, Yi 2011. Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation. PloS one, 6 3, e18002Kurtulus, Sema; Tripathi, Pulak; Moreno-Fernandez, Maria E; Sholl, Allyson; Katz, Jonathan D; Grimes, H Leighton; Hildeman, David A 2011. Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim. Journal of immunology (Baltimore, Md. : 1950), 186 10, 5729-37McClendon, A Kathleen; Dean, Jeffry L; Ertel, Adam; Fu, Zhiyan; Rivadeneira, Dayana B; Reed, Christopher A; Bourgo, Ryan J; Witkiewicz, Agnieszka; Addya, Sankar; Mayhew, Christopher N; Grimes, H Leighton; Fortina, Paolo; Knudsen, Erik S 2011. RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage. Gastroenterology, 141 4, 1439-50Barnes, Michael J; Aksoylar, Halil; Krebs, Philippe; Bourdeau, Tristan; Arnold, Carrie N; Xia, Yu; Khovananth, Kevin; Engel, Isaac; Sovath, Sosathya; Lampe, Kristin; Laws, Eleana; Saunders, Amy; Butcher, Geoffrey W; Kronenberg, Mitchell; Steinbrecher, Kris; Hildeman, David; Grimes, H Leighton; Beutler, Bruce; Hoebe, Kasper 2010. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice. Journal of immunology (Baltimore, Md. : 1950), 184 7, 3743-54Guo, Fukun; Hildeman, David; Tripathi, Pulak; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi 2010. Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 107 43, 18505-10Kong, Kimi Y; Owens, Kristin S; Rogers, Jason H; Mullenix, Jason; Velu, Chinavenmeni S; Grimes, H Leighton; Dahl, Richard 2010. MIR-23A microRNA cluster inhibits B-cell development. Experimental hematology, 38 8, 629-640.e1Meyer, Sara E; Hasenstein, Jason R; Baktula, Avinash; Velu, Chinavenmani S; Xu, Yan; Wan, Huajing; Whitsett, Jeffrey A; Gilks, C Blake; Grimes, H Leighton 2010. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. The American journal of pathology, 177 3, 1503-13Phelan, James D; Shroyer, Noah F; Cook, Tiffany; Gebelein, Brian; Grimes, H Leighton 2010. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Current opinion in hematology, 17 4, 300-7Sharif-Askari, Ehssan; Vassen, Lothar; Kosan, Christian; Khandanpour, Cyrus; Gaudreau, Marie-Claude; Heyd, Florian; Okayama, Taro; Jin, Jianmin; Rojas, Meghan E B; Grimes, H Leighton; Zeng, Hui; Möröy, Tarik 2010. Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65. Molecular and cellular biology, 30 16, 3929-42Tripathi, Pulak; Kurtulus, Sema; Wojciechowski, Sara; Sholl, Allyson; Hoebe, Kasper; Morris, Suzanne C; Finkelman, Fred D; Grimes, H Leighton; Hildeman, David A 2010. STAT5 is critical to maintain effector CD8+ T cell responses. Journal of immunology (Baltimore, Md. : 1950), 185 4, 2116-24Arumugam, Paritha I; Urbinati, Fabrizia; Velu, Chinavenmeni S; Higashimoto, Tomoyasu; Grimes, H Leighton; Malik, Punam 2009. The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity. PloS one, 4 9, e6995Gu, YuanYuan; Harley, Isaac T W; Henderson, Lindsay B; Aronow, Bruce J; Vietor, Ilja; Huber, Lukas A; Harley, John B; Kilpatrick, Jeffrey R; Langefeld, Carl D; Williams, Adrienne H; Jegga, Anil G; Chen, Jing; Wills-Karp, Marsha; Arshad, S Hasan; Ewart, Susan L; Thio, Chloe L; Flick, Leah M; Filippi, Marie-Dominique; Grimes, H Leighton; Drumm, Mitchell L; Cutting, Garry R; Knowles, Michael R; Karp, Christopher L 2009. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature, 458 7241, 1039-42Guo, Fukun; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi 2009. 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