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Jun Lu, PhD

Associate Professor Tenure

Contact Information

Jun Lu, PhD

Mailing Address

  • 10 Amistad St, AMISB-237C

    New Haven, CT, 06520-8005

    United States

Lu Lab @ Yale

Research Summary

We are interested in noncoding and epigenetic regulation of hematopoiesis and cancer. Currently, we are focusing on 1. Epigenetic mechanisms that control solid cancer and immune cell cross talks, 2. Noncoding RNAs in normal hematopoiesis and leukemia, 3. Finding novel functional noncoding sequences in the genome.

Extensive Research Description

The completion of the human genome project leads to the realization that only a small percentage of our heritable DNA sequences encodes proteins. Instead of being “junk DNA”, a significant portion of the noncoding genome has functions, in the forms of non-coding RNAs, binding sites for protein factors or other functional sequences. These noncoding elements often cross-talk with epigenetic machinery to regulate cell fate and behavior.

In our laboratory, we use the amazing blood-forming system, or hematopoiesis, as a model to study the noncoding and epigenetic controls. In a normal adult human being, ~100 to 200 billion new blood cells are generated every day to replace similar numbers of existing blood cells. These mature blood cells originate from hematopoietic stem cells and exhibit vastly different forms, shapes and functions, regulating processes such as innate and adaptive immune responses, oxygen transport and coagulation. Mature blood cells, such as macrophages and neutrophils, can also be found in tumor tissues to control tumor cell behavior and anti-cancer immune responses. During aging, hematopoietic stem cells accumulate mutations in key tumor suppressor genes, most frequently those regulating DNA methylation. Mutant hematopoietic stem cells out-compete normal stem cells in a process termed clonal hematopoiesis. Clonal hematopoiesis is a near universal feature of human aging, increases the risk of diseases such as leukemia, and can have wider impacts on other aging-associated diseases such as vascular defects and solid cancer.

The fascinating biology discussed above raises a number of intriguing questions that we are addressing in our lab. What regulates the cross-talk between cancer cells and hematopoietic cells? What regulates the competition between clones of hematopoietic stem cells? What regulates the transformation of normal hematopoietic stem cell into malignant cells? How is the speed of hematopoietic regeneration regulated? What controls the form and function of mature blood cells?


Coauthors

Research Interests

Cell Differentiation; Hematologic Diseases; Hematopoiesis; Neoplasms; Cell Lineage

Selected Publications

  • The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression.Pan W, Zhu S, Qu K, Meeth K, Cheng J, He K, Ma H, Liao Y, Wen X, Roden C, Tobiasova Z, Wei Z, Zhao J, Liu J, Zheng J, Guo B, Khan SA, Bosenberg M, Flavell RA, Lu J. The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression. Immunity 2017, 47:284-297.e5.
  • Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation.Roden C, Gaillard J, Kanoria S, Rennie W, Barish S, Cheng J, Pan W, Liu J, Cotsapas C, Ding Y, Lu J. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Research 2017, 27:374-384.
  • A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions.Cheng J, Roden CA, Pan W, Zhu S, Baccei A, Pan X, Jiang T, Kluger Y, Weissman SM, Guo S, Flavell RA, Ding Y, Lu J. A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions. Nature Communications 2016, 7:11178.
  • miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism.Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism. Blood 2017, 129:1491-1502.
  • Nonstochastic reprogramming from a privileged somatic cell state.Guo S, Zi X, Schulz VP, Cheng J, Zhong M, Koochaki SH, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. Nonstochastic reprogramming from a privileged somatic cell state. Cell 2014, 156:649-62.
  • An extensive network of TET2-targeting MicroRNAs regulates malignant hematopoiesis.Cheng J, Guo S, Chen S, Mastriano SJ, Liu C, D'Alessio AC, Hysolli E, Guo Y, Yao H, Megyola CM, Li D, Liu J, Pan W, Roden CA, Zhou XL, Heydari K, Chen J, Park IH, Ding Y, Zhang Y, Lu J. An extensive network of TET2-targeting MicroRNAs regulates malignant hematopoiesis. Cell Reports 2013, 5:471-81.
  • An in vivo functional screen uncovers miR-150-mediated regulation of hematopoietic injury response.Adams BD, Guo S, Bai H, Guo Y, Megyola CM, Cheng J, Heydari K, Xiao C, Reddy EP, Lu J. An in vivo functional screen uncovers miR-150-mediated regulation of hematopoietic injury response. Cell Reports 2012, 2:1048-60.
  • Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms.Guo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109:16636-41.
  • MicroRNA expression profiles classify human cancers.Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-8.
  • MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors.Lu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH, Dombkowski DM, Preffer FI, Scadden DT, Golub TR. MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Developmental Cell 2008, 14:843-53.
  • Distinct microRNA expression profiles in acute myeloid leukemia with common translocations.Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z, Neilly MB, Jin J, Zhang Y, Bohlander SK, Zhang DE, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD, Chen J. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105:15535-40.
  • MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia.Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD, Chen J. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104:19971-6.
  • MicroRNA miR-125a controls hematopoietic stem cell number.Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, Purton LE, Fleming HH, Cobb B, Merkenschlager M, Golub TR, Scadden DT. MicroRNA miR-125a controls hematopoietic stem cell number. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107:14229-34.
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