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Dr. Ellen Puré speaks at the Ralph L. Brinster President’s Distinguished Professorship reception

News & Events in Biomedical Sciences


Grant Highlight

Dr. Andres Blanco, Penn VetDr. M. Andres Blanco has been awarded a grant from the Margaret Q. Landenberger Research Foundation, in the amount of $200,000 over two years to study “Investigating the role of KAT6A as a differentiation therapy target MLL-rearranged acute myeloid leukemia”.

This project builds on our previous work that uncovered the histone acetyltransferase KAT6A and the histone binding protein ENL as drivers of transcriptional programs sustaining the stemness and proliferation of acute myeloid leukemia (AML) cells. The overall goal of the funded project is to understand the molecular mechanisms by which KAT6A and ENL cooperatively establish and maintain oncogene promoters in highly activate states. Our findings will advance the understanding of how leukemogenic gene expression programs are orchestrated, and will also help determine the contexts in which small molecule inhibition of KAT6A and/or ENL could serve as a potential therapeutic strategy in AML.


Biomedical Sciences News

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Changing the identity of cancer cells to eliminate them

A team led by the School of Veterinary Medicine’s M. Andrés Blanco has uncovered a new target for treating certain blood cancers that works by removing an obstacle to their maturation.

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Protein’s ‘silent code’ affects how cells move

The protein actin is ubiquitous and essential for life. In mammals, every cell expresses two of its forms, beta-actin and gamma-nonmuscle-actin. Despite having distinct roles, the two forms are nearly identical, sharing 99% of their amino acid sequence.

Pinpointing how cancer cells turn aggressive-Dr. Christopher Lengner Lab

Pinpointing how cancer cells turn aggressive

Penn scientists have developed a new method for tracing the lineage and gene expression patterns of metastatic cancer at the single-cell level.

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A new role for a triple-negative breast cancer target

These changes require energy. In a study using a new, genetically altered mouse model, researchers led by Rumela Chakrabarti of Penn’s School of Veterinary Medicine have uncovered a key protein involved in supplying the mammary gland with fuel during puberty. It’s a protein that her group had earlier shown to play a role in triple-negative breast cancer (TNBC), a particularly aggressive form of the disease

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Lung cell transplant boosts healing after the flu

Some cases of the flu are so severe they cause lasting injury to the lungs. New research from the University of Pennsylvania now points to a strategy that may one day offer protection against this damage.


Events


Publications

Recent publications from the labs of Biomedical Sciences.

  • Wang J, Syrett C, Kramer M, Basu A, Atchison M, and Anguera M. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. PNAS 2016; published ahead of print March 21, 2016, doi:10.1073/pnas.1520113113
  • Lo A, Wang LC, Scholler J, Monslow J, Avery D, Newick K, O’Brien S, Evans RA, Bajor DJ, Clendenin C, Durham AC, Buza EL, Vonderheide RH, June CH, Albelda SM, Puré E. Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res. 2015 75(14):2800-10.
  • Ozek C, Zimmer DJ, De Jonghe BC, Kalb RG, Bence KK.  Ablation of intact hypothalamic and/or hindbrain TrkB signaling leads to perturbations in energy balance.  Molecular Metabolism. 18 August 2015 In press.
  • Yang F, Leu NA, Oates R, Silber S, Marszalek JD, Skaletsky H, Brown LG, Rozen S, Page DC, Wang PJ. TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. EMBO Molecular Medicine. 2015 7(9):1198-1210.
  • Zhou J, Stein P, Chmatal L, Leu NA, Xue J, Ma J, Huang X, Lampson M, Schultz RM, and Wang PJ. Accelerated reproductive aging in females lacking a novel centromere protein SYCP2L. Hum. Mol. Genetics. 2015. In press.
  •  Zhang F, Patel D, Colavita K, Rodionova I,  Buckley B, Scott D,  Kumar A, Shabalina SA, Saha S, Chernov M, Osterman A, and Kashina, A. (2015) Arginylation Regulates Purine Biosynthesis by Facilitating the Biological Activity of Phosphorybosyl Pyrophospate Synthase. Nature Communications 6:7517 doi: 10.1038/ncomms8517. In press.
  • Vourekas A, Zheng K, Fu Q, Maragkakis M, Alexiou P, Ma J, Pillai RS, Mourelatos Z, and Wang, PJ. MOV10L1 binds piRNA precursors to initiate piRNA processing. Genes and Development. In press.
  • Suzuki D, Sahu R, Leu NA, Senoo M. The carboxy-terminus of p63 links cell cycle control and the proliferative potential of epidermal progenitor cells. Development. Dec 11, 2014; pii: dev.118307 [Epub ahead of print]. PMID: 25503409.
  • Banerjee S, Das RK, and Shapiro BH. Growth hormone-independent suppression of growth hormone-dependent female isoforms of cytochrome P450 by the somatostatin analog octreotide.  Eur J Pharmacol. Sep 5, 2013; 715(0): 256–261. PMCID: PMC375958
  • Moon, E., L.C. Wang, D.V. Dolfi, C.B. Wilson, R. Ranganathan, J. Sun, V. Kapoor, E. Puré, M.C. Milone, C.H. June, J. Riley, E.J. Wherry, S.M. Alblelda. 2014. Multifactorial T cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor transduced human T cells. Clin. Cancer Res. Epub ahead of print. PMID:24919573.
  • Dong DW, Pereira F, Barrett SP, Kolesar JE, Cao K, Damas J, Yatsunyk LA, Johnson FB, Kaufman BA. Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints. BMC Genomics. 2014 Aug 13;15(1):677 PMID:  25124333
  • Epperson CN, Kim DR, Bale TL. Estradiol modulation of monoamine metabolism: one possible mechanism underlying sex differences in risk for depression and dementia. JAMA Psychiatry. 2014 Aug 1;71(8):869-70. PMCID:  PMC4126841
  • Yildirim O, Hung JH, Cedeno RJ, Weng Z, Lengner CJ, Rando OJ. A System for Genome-Wide Histone Variant Dynamics In ES Cells Reveals Dynamic MacroH2A2 Replacement at Promoters. PLoS Genet. 2014 Aug 7;10(8):e1004515 PMCID:  PMC4125097
  • Zhou J, Goldberg EM, Leu NA, Zhou L, Coulter DA, Wang PJ. Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1 deletion syndrome. Hum Mol Genet. 2014 Jul 15;23(14):3823-9. PMCID:  PMC4065155
  • Cornachione AS, Leite FS, Wang J, Leu NA, Kalganov A, Volgin D, Han X, Xu T, Cheng YS, Yates JR 3rd, Rassier DE, Kashina A. Arginylation of myosin heavy chain regulates skeletal muscle strength.  Cell Reports. 2014 Jul 24;8(2):470-6.
  • Howerton CL, Bale TL. Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9639-44. PMCID:  PMC4084439
  • Gray CM, McCorkell KA, Chunduru SK, McKinlay MA, May MJ.  Negative feedback regulation of NF-κB-inducing kinase is proteasome-dependent but does not require cellular inhibitors of apoptosis. Biochem Biophys Res Commun. 2014 Jul 18;450(1):341-6. PMCID:  PMC4107106
  • Habineza Ndikuyeze G, Gaurnier-Hausser A, Patel R, Baldwin AS, May MJ, Flood P, Krick E, Propert KJ, Mason NJ. A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma. PLoS One. 2014 May 5;9(5):e95404 PMCID:  PMC4010398
  • Das RK, Banerjee S, Shapiro BH. Irreversible perinatal imprinting of adult expression of the principal sex-dependent drug-metabolizing enzyme CYP2C11. FASEB J. 2014 Jun 18. pii: fj.13-248864. PMCID:  PMC4139898
  • Suzuki D, Leu NA, Brice AK, Senoo M. Expression analysis of Dact1 in mice using a LacZ reporter. Gene Expr Patterns. 2014 May;15(1):21-30. PMID:  24681206
  • Maria A. Lim, Kendra K. Bence, Ishani Sandesara, Penelope Andreux, Johan Auwerx, Jeff Ishibashi, Patrick Seale, and Robert G. Kalb.  Genetically altering organismal metabolism by leptin-deficiency benefits a mouse model of Amyotrophic Lateral Sclerosis.  Human Molecular Genetics, May 15th, 2014, PMID: 24833719.
  • Howerton AR, Roland AV, Bale TL. Dorsal raphe neuroinflammation promotes dramatic behavioral stress dysregulation. J Neurosci. 2014 May 21;34(21):7113-23. PMCID:  PMC4028491
  • Morrison KE, Rodgers AB, Morgan CP, Bale TL. Epigenetic mechanisms in pubertal brain maturation. Neuroscience. 2014 Apr 4;264:17-24. PMCID:  PMC3959229.
  • Rukhadze I, Kalter J, Stettner GM, Kubin L. Lingual muscle activity across sleep-wake States in rats with surgically altered upper airway. Front Neurol. 2014 Apr 28;5:61. PMCID:  PMC4009435
  • Bansal S, Leu AN, Gonzalez FJ, Guengerich FP, Chowdhury AR, Anandatheerthavarada HK, Avadhani NG.  Mitochondrial targeting of cytochrome P450 (CYP) 1B1 and its role in polycyclic aromatic hydrocarbon-induced mitochondrial dysfunction. J Biol Chem. 2014 Apr 4;289(14):9936-51. PMCID:  PMC3975038
  • Bhattacharya S, Katlinski KV, Reichert M, Takano S, Brice A, Zhao B, Yu Q, Zheng H, Carbone CJ, Katlinskaya YV, Leu NA, McCorkell KA, Srinivasan S, Girondo M, Rui H, May MJ, Avadhani NG, Rustgi AK, Fuchs SY. Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury.  EMBO Mol Med. 2014 Mar;6(3):384-97. PMCID:   PMC3958312
  • Gray CM, Remouchamps C, McCorkell KA, Solt LA, Dejardin E, Orange JS, May MJ. Noncanonical NF-κB signaling is limited by classical NF-κB activity. Sci Signal. 2014 Feb 4;7(311):ra13 PMCID:  PMC3960999
  • Basu A, Wilkinson FH, Colavita K, Fennelly C, Atchison ML. YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment. Nucleic Acids Res. 2014 Feb;42(4):2208-23. PMCID:  PMC3936737
  • Fu Q, Wang PJ. Mammalian piRNAs: Biogenesis, function, and mysteries. Spermatogenesis. 2014 Feb 7;4:e27889. PMCID:  PMC4114582
  • Ryan C. Tsou, Kimberly S. Rak, Derek J. Zimmer, and Kendra K. Bence.  Improved metabolic phenotype of hypothalamic PTP1B-deficiency is dependent upon the leptin receptor.  Molecular Metabolism,  Volume 3, issue 3, pages 301-312 (epub Jan. 2014). PMCID: PMC3986631.

BMS Seminars & Conferences

  • Check back soon for upcoming lectures, seminars and conferences.

  • 03/21/2016: Dr. Montserrat Anguera's recently published work in the Proceedings of the National Academy of Sciences was featured in Penn News. The paper, titled "Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X," offers a mechanistic explanation for the female bias in autoimmune diseases.  Read more...

  • The Department of Biomedical Sciences welcomes Dr. Rumela Chakrabarti. Dr. Chakrabarti, who earned her PhD in Cellular and Molecular Biology from Kent State University, joins us from Princeton University.  Her areas of interest include the tumor suppressive role of Elf5 in different subtypes of breast cancer, the identification of genes and pathways in preneoplastic mammary gland and tumors affected by Elf5 loss, and the evaluation of the pathological role of loss of Elf5 in human patient-derived xenograft (PDX) tumors.

  • 06/17/2015: Dr. Tracy Bale's recent paper was featured in Penn News Today.  The new work, published in Endocrinology, suggests that the maternal vaginal microbiome is one of the ways that a mother’s stress during pregnancy can “reprogram” the developing brains of her children. In addition to Dr. Bale, the study was conducted by postdoctoral researchers Eldin Jašarević and Christopher Howerton and research specialist Christopher Howard, all from the Bale lab. Read the article...

  •  03/20/2015: Dr. Chris Lengner, along with other Penn collaborators, has found evidence of a potential cause of colon cancer,  a protein called MSI2. Dr. Lengner is the senior author on a paper published in Nature Communications, which describes their findings. Read the article...

  • 03/04/2015:  Dr. Jeremy Wang, along with other Penn collaborators, published a paper describing the function of an enzyme critical to male fertility in Genes and Development. Read the article...

  • 08/27/2014: Dr. Peter Dodson and Brandon Hedrick featured on Philly.com for their work on a nest of fossilized juvenile dinosaurs.  Read the article...

  • 04/10/2014: Dr. Kendra Bence's work on obesity and related diseases featured in Penn Current.  Read the article...

  • 03/13/2014: Dr. Jeremy Wang's work with the Children's Hospital of Philadelphia featured in Penn Current.  Read the article...