Blais University Chair in Molecular Medicine
Potential Rotation Projects: There are numerous potential rotation project available in the Mello lab: Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.
The project aims to develop computational algorithms and software programs for analyzing high-throughput sequence data such as ChIP-Seq RNA-Seq small RNA sequencing data. PhD required. A strong background in computational biology especially experience with analyzing high-throughput sequencing data is highly desirable. Excellent communication and writing skills and the ability to work with experimental and computational collaborators are essential. To apply please forward CV cover letter and three references to: Zhiping.Weng@umassmed.edu
Please contact Dr. Weng for information on rotations that are available in her lab.
David J. Freelander Memorial Professor in AIDS Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Theurkauf for additional details.
Rotation Projects Proper control of cell division and accurate chromosome segregation are fundamental to cell function and normal development. Chromosome segregation errors lead to birth defects, and abnormal cell division control is associated with essentially all cancers. A major aim of research in the laboratory is to understand cell cycle control and chromosome segregation mechanisms. We use a combination of classical and molecular genetics, high-resolution in vivo imaging, and biochemical techniques to define pathways that control the cell cycle and chromosome segregation in response to environmental insult (DNA damaging agents) and developmental queues. Rotation projects focus on the role of cell cycle checkpoint and tumor suppressor pathways during the earliest stages of embryogenesis, and cell cycle control of actin and microtubule reorganization during mitosis. Through these projects, students gain exposure of the art in vivo imaging and genetic and molecular manipulations of gene function to define pathways controlling cell division and chromosome segregation. Embryonic Patterning Essentially all cells are asymmetric, with structurally distinct surfaces and polarized internal organization. This asymmetry is essential to the specialized functions cells serve within complex multi-cellular organisms . A second area of interest focuses on the mechanisms that establish cellular asymmetry. In Drosophila, the embryonic axes are specified during oogenesis through the asymmetric localization of key morphogenetic molecules within the developing oocyte. We use axis specification in the fly as a model for the processes that establish cellular asymmetry. An intact microtubule network is essential to axis specification in the fly oocyte and to polarization of somatic. We hope to define the molecular functions for microtubules in establishing cellular asymmetry. We are currently using in vivo imaging techniques to directly characterize the microtubule dependent mRNA transport processes that differentiate the anterior and posterior poles of the developing oocyte. In addition, classical genetic and biochemical techniques are used to identify the microtubule motors and associated proteins that mediate mRNA movements to the oocyte poles.
Remondi Family Chair in Biomedical Research
POSTDOCTORAL POSITION: RNAI PRECLINICAL DEVELOPMENT Excellent training opportunity for a person considering industrial carrier in drug development Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several classes of oligonucleotides which can efficiently silence genes in various tissues with acceptable level of toxicity. There are also new chemistries being developed to further improve oligonucleotide tissue distribution and cellular uptake. The successful candidate will be a key part of an intra-disciplinary team working with biologists and chemists to develop novel types of therapeutics for treatment of neurological disease, liver disease and orphan indications. The work will include compounds identification, screening, characterization, in vivo efficacy and PK/PD studies, novel assays development etc. In addition exposure and training in nucleic acid pre-clinical development, project management etc will be provided. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular cell biology or pharmacology.
RNAI MEDICINAL CHEMISTRY/ RNA OLIGONUCLEOTIDE CHEMISTRY Develop and characterize novel RNA chemistries to promote efficient oligonucleotide internalization and tissue distribution. Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several chemistries and formulations developed by us and others that effectively support oligo internalization and favorable PK/PD. In most cases in vivo efficacy is limited by (1) poor PK (2) inefficient tissue distribution (3) compound entrapment in biologically inactive intracellular compartments. The objective of future studies will be development of novel chemistries, which promote receptor mediated cellular internalization and/ or endosomal escape. The successful candidate will be responsible for the design and synthesis of novel RNA precursors, optimization of RNA synthesis and conjugation protocols and interface with the biology part of the lab. In addition, exposure to pre-clinical development programs and oligonucleotide manufacturing will be available. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and have previous experience in nucleic acid / oligonucleotide chemistry.
SMALL RNA TRAFFICKING Discover, characterize and adapt mechanisms of small RNA extracellular and intracellular trafficking for development of novel classes of oligonucleotide drugs. A serious limitation in realizing the potential of oligonucleotide based therapies has been the exceedingly inefficient transit of oligonucleotides from outside cells to the intracellular compartments where the biologically relevant activity happens. On the other hand, there are multiple lines of evidence supporting the notion that nature has implemented evolutionarily conserved mechanisms and pathways for efficiently trafficking small RNAs across cellular boundaries. The objective of future studies will be the systematic evaluation of mechanisms of cellular uptake of different classes of oligonucleotides and their comparison to mechanisms of native RNA trafficking using a combination of experimental approaches, including advanced RNA chemistry and high temporal and spatial resolution microscopy in living cells, Mass spectrometry, cell biology and others. The successful candidate will work closely with Victor Ambros and Silvia Corvera labs and the UMASS imaging group and receive training in RNA chemistry, biochemistry, cell biology and pre-clinical development. QUALIFICATIONS:Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular and cell biology
Our laboratory uses a combination of nucleic acid and oligonucleotide chemistry, biochemistry, cell biology, and pharmacology and develops and evaluate novel technologies for development of oligonucleotide therapeutics. A rotation project is available to develop and identify chemically modified self-delivering RNAi compounds for treatment of Huntington and other diseases.
Gretchen Stone Cook Chair in Biomedical Sciences
A postdoctoral position is available to study in this laboratory. Contact Dr. Zamore for additional details
Potential Rotation Projects Our laboratory uses a combination of biochemistry, cell biology, and genetics to dissect the RNAi pathway. A rotation project is available to explore the mechanisms that underlie the RNAi phenomenon or the biological pathways in which RNAi enzymes participate in flies, mice and humans.
Zhang G, Tu S, Yu T, Zhang XO, Parhad SS, Weng Z, Theurkauf WE
Zhang G, Tu S, Yu T, Zhang XO, Parhad SS, Weng Z, Theurkauf WE. Co-dependent Assembly of Drosophila piRNA Precursor Complexes and piRNA Cluster Heterochromatin. Cell Rep. 2018 09 25; 24(13):3413-3422.e4.
Co-dependent Assembly of Drosophila piRNA Precursor Complexes and piRNA Cluster Heterochromatin.
Wet-lab and Bioinformatic postdoctoral fellow positions are available for candidates with recent Ph.D. or M.D./Ph.D. degrees in Molecular Biology, Neuroscience, Genetics, Genomics, Cell Biology, or related fields. They should be highly motivated, have a strong desire to learn, and excellent communication skills. Applicants should send their CV, summary of previous research and the name of three references to Dr. Michael Lodato.
Rotations will revolve around studying somatic mutations in the normal brain, in the diseased brain, and outside of the brain using single-cell genomics. Please contact Dr. Lodato for details.
Yu T, Koppetsch BS, Pagliarani S, Johnston S, Silverstein NJ, Luban J, Chappell K, Weng Z, Theurkauf WE
Yu T, Koppetsch BS, Pagliarani S, Johnston S, Silverstein NJ, Luban J, Chappell K, Weng Z, Theurkauf WE. The piRNA Response to Retroviral Invasion of the Koala Genome. Cell. 2019 10 17; 179(3):632-643.e12.
The piRNA Response to Retroviral Invasion of the Koala Genome.
?zata DM, Yu T, Mou H, Gainetdinov I, Colpan C, Cecchini K, Kaymaz Y, Wu PH, Fan K, Kucukural A, Weng Z, Zamore PD
?zata DM, Yu T, Mou H, Gainetdinov I, Colpan C, Cecchini K, Kaymaz Y, Wu PH, Fan K, Kucukural A, Weng Z, Zamore PD. Evolutionarily conserved pachytene piRNA loci are highly divergent among modern humans. Nat Ecol Evol. 2020 01; 4(1):156-168.
Evolutionarily conserved pachytene piRNA loci are highly divergent among modern humans.
Parhad SS, Yu T, Zhang G, Rice NP, Weng Z, Theurkauf WE
Parhad SS, Yu T, Zhang G, Rice NP, Weng Z, Theurkauf WE. Adaptive Evolution Targets a piRNA Precursor Transcription Network. Cell Rep. 2020 02 25; 30(8):2672-2685.e5.
Adaptive Evolution Targets a piRNA Precursor Transcription Network.
Smith JL, Rodr?guez TC, Mou H, Kwan SY, Pratt H, Zhang XO, Cao Y, Liang S, Ozata DM, Yu T, Yin Q, Hazeltine M, Weng Z, Sontheimer EJ, Xue W
Smith JL, Rodr?guez TC, Mou H, Kwan SY, Pratt H, Zhang XO, Cao Y, Liang S, Ozata DM, Yu T, Yin Q, Hazeltine M, Weng Z, Sontheimer EJ, Xue W. YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte-Like Cells. Hepatology. 2021 03; 73(3):1011-1027.
YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte-Like Cells.
Wu PH, Fu Y, Cecchini K, ?zata DM, Arif A, Yu T, Colpan C, Gainetdinov I, Weng Z, Zamore PD
Wu PH, Fu Y, Cecchini K, ?zata DM, Arif A, Yu T, Colpan C, Gainetdinov I, Weng Z, Zamore PD. The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. Nat Genet. 2020 07; 52(7):728-739.
The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility.
Zhang G, Yu T, Parhad SS, Ho S, Weng Z, Theurkauf WE
Zhang G, Yu T, Parhad SS, Ho S, Weng Z, Theurkauf WE. piRNA-independent transposon silencing by the Drosophila THO complex. Dev Cell. 2021 09 27; 56(18):2623-2635.e5.
piRNA-independent transposon silencing by the Drosophila THO complex.
Cecchini K, Biasini A, Yu T, S?flund M, Mou H, Arif A, Eghbali A, Colpan C, Gainetdinov I, de Rooij DG, Weng Z, Zamore PD, ?zata DM
Cecchini K, Biasini A, Yu T, S?flund M, Mou H, Arif A, Eghbali A, Colpan C, Gainetdinov I, de Rooij DG, Weng Z, Zamore PD, ?zata DM. The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice. Reproduction. 2023 02 01; 165(2):183-196.
The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice.
Ho S, Rice NP, Yu T, Weng Z, Theurkauf WE
bioRxiv : the preprint server for biology
Ho S, Rice NP, Yu T, Weng Z, Theurkauf WE. Aub, Vasa and Armi localization to phase separated nuage is dispensable for piRNA biogenesis and transposon silencing in Drosophila. bioRxiv. 2023 Jul 26.
Aub, Vasa and Armi localization to phase separated nuage is dispensable for piRNA biogenesis and transposon silencing in Drosophila.
Jeffries AM, Yu T, Ziegenfuss JS, Tolles AK, Kim Y, Weng Z, Lodato MA
Jeffries AM, Yu T, Ziegenfuss JS, Tolles AK, Kim Y, Weng Z, Lodato MA. Single-cell transcriptomic and genomic changes in the aging human brain. bioRxiv. 2023 Nov 07.
Single-cell transcriptomic and genomic changes in the aging human brain.
Yu T, Blyton MBJ, Koppetsch BS, Abajorga M, Luban J, Chappell K, Theurkauf WE, Weng Z
Yu T, Blyton MBJ, Koppetsch BS, Abajorga M, Luban J, Chappell K, Theurkauf WE, Weng Z. The Trajectory of KoRV-A Evolution Indicates Initial Integration into the Koala Germline Genome Near Coffs Harbour. Res Sq. 2024 Dec 23.
The Trajectory of KoRV-A Evolution Indicates Initial Integration into the Koala Germline Genome Near Coffs Harbour.
Yu T, Blyton MBJ, Abajorga M, Koppetsch BS, Ho S, Xu B, Hu Z, Luban J, Chappell K, Weng Z, Theurkauf WE
Yu T, Blyton MBJ, Abajorga M, Koppetsch BS, Ho S, Xu B, Hu Z, Luban J, Chappell K, Weng Z, Theurkauf WE. Evolution of KoRV-A transcriptional silencing in wild koalas. Cell. 2025 Apr 17; 188(8):2081-2093.e16.
Evolution of KoRV-A transcriptional silencing in wild koalas.
Gustafsson HT, Ferguson L, Galan C, Yu T, Upton H, Kaymak E, Weng Z, Collins K, Rando OJ
Gustafsson HT, Ferguson L, Galan C, Yu T, Upton H, Kaymak E, Weng Z, Collins K, Rando OJ. Deep sequencing of yeast and mouse tRNAs and tRNA fragments using OTTR. Elife. 2025 Apr 25; 14.
Deep sequencing of yeast and mouse tRNAs and tRNA fragments using OTTR.
Jeffries AM, Yu T, Ziegenfuss JS, Tolles AK, Baer CE, Sotelo CB, Kim Y, Weng Z, Lodato MA
Jeffries AM, Yu T, Ziegenfuss JS, Tolles AK, Baer CE, Sotelo CB, Kim Y, Weng Z, Lodato MA. Single-cell transcriptomic and genomic changes in the ageing human brain. Nature. 2025 Oct; 646(8085):657-666.
Single-cell transcriptomic and genomic changes in the ageing human brain.