Dr Padma Sheela Jayaraman PhD

Dr Padma Sheela Jayaraman

Institute of Cancer and Genomic Sciences
Senior Lecturer in Cancer Biology

Contact details

Address
Institute of Cancer and Genomic Sciences
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Sheela Jayaraman is a Senior  Research Group Leader at the Institute of Cancer and Genomic Sciences. Sheela has an interest is in understanding the role of proteins known as transcription factors in cancer biology and in angiogenesis. She uses a variety of methods to do this including mammalian cell culture, cDNA microarrays, RNAseq, ChIP and ChIPseq, biophysical experiments, and animal models of tumour growth and tumour spread. This variety of methods allows the most complete  understanding of  the role of these proteins in  tumour cells and in the whole animal.’

Sheela was awarded a Birmingham Senior Stem Cell Fellowship to establish her group and is currently a Senior Lecturer within the Institute. Sheela undertakes research in a variety of cancer types including leukaemia, breast cancer, prostate cancer and bile duct/liver cancer. She is supported by awards from Breast Cancer Now, British Heart Foundation and the Medical Research Council.  

Qualifications

  • Ph.D Gene Regulation, University of Birmingham 1989
  • BSc Hons Biochemistry, University of  London 1985

Biography

Sheela qualified with a Ph.D Biochemistry from the University of Birmingham. She then took up a Post Doctoral Fellowship  in London at the Marie Curie Research Institute where she worked in the Cell Signalling and Gene Regulation Laboratory with Dr. C. Goding. Following that she undertook a second Post Doctoral Fellowship with Dr. G. Goodwin at the Institute Cancer Research. She was subsequently  awarded a MRC Career Development Award (1996) and was a Research Fellow and Senior Research Fellow at Bristol University. In 2006 Sheela moved to the University of Birmingham where she was awarded a Senior Stem Cell Research Fellowship to continue her work on the role of gene regulation by PRH in leukaemia and in other cancers. In 2009 Sheela became a Senior Lecturer in Cancer Biology and is continuing her work in a variety of cancers and vascular cell types.

Teaching

  • Module Lead on New Targets in Cancer BMedSci
  • Lecturer on Stem Cells in BMedSci
  • Tutorials in First and Second Year BMedSci
  • Mentor for Medical students Years 1-5

Postgraduate supervision

Dr. Sheela Jayaraman has supervised 9 Ph.D students to completion of studies within four years. All students have published and several students are currently in academia as post-doctoral fellows, principal investigators or in industry as research scientists or research analysts. She has also supervised intercalating medical students, Clincial Fellows and many MSc students.

Research

My major interest is in how cancer cells proliferate and progress toward an invasive phenotype resulting in cancer metastasis. To understand this process I have investigated the activity of a growth regulatory protein and transcription factor known as PRH/HHEX. This protein is involved in the regulation of proliferation, differentiation, migration and invasion of many cell types. To understand how PRH works in these processes my laboratory has investigated and  published a number of papers on the biophysical characterisation of the PRH protein and the mechanisms that PRH uses to regulate genes. I also investigate the post-translational regulation of the PRH protein and I have shown shown that phosphorylation of PRH can  control both leukaemic and epithelial  cancer  cell growth and migration. Since many of  the pathways that PRH controls, including for example the VEGF signalling pathway, are common to many cell types my research involves a variety of different cancer types. My recent research has focused on the regulation of cancer stem cell growth by PRH in  breast cancer and in bile duct cancer.

In collaboration with other research groups in the USA and at the University of Bristol my laboratory also studies the role of PRH in the vascular compartment and the part it plays in intimal thickening and cardiac disease.

Other activities

  • Member of European Association of Cancer Research
  • Member of British Association of Cancer Research
  • Member of Biochemical Society
  • Previously Editor of Biochemical Journal 

Publications

CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation. Siddiqui YH, Kershaw RM, Humphreys EH, Marcolino de Assis Junior E, Chaudhri S, Padma-Jayaraman PS  and Gaston K. Oncogenesis 2017 Jan 30;6(1):e293. doi: 10.1038/oncsis.2016.82.

Urokinase-type plasminogen activator (uPA) promotes angiogenesis by attenuating Proline-rich homeodomain protein (PRH) transcription factor activity and de-repressing vascular endothelial growth factor (VEGF) receptor expression.  Stepanova V, Jayaraman PS, Zaitsev SV, Lebedeva T, Bdeir K, Kershaw R, Holman KR Parfyonova YV, Semina EV, Beloglazova EB, Tkachuk VA, and Cines, DB.  Journal of Biological Chemistry 2016 Jul 15;291(29):15029-45. doi: 1074/jbc.M115.678490 

Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion.  Gaston K, Tsitsilianos MA, Wadey K and Jayaraman PS. Cell and Bioscience  2016 6:12 DOI 10.1186/s13578-016-0077-7.

PRH/Hhex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Kershaw, R M. Siddiqui Y H, Roberts, D., Jayaraman PS, and Gaston K.  Oncogene  2014 Dec 4;33(49):5592-600. doi: 10.1038/onc.2013.496..

Proline Rich Homeodomain (PRH/HHEX) protein in the control of haematopoiesis and myeloid cell proliferation and its potential as a therapeutic target in myeloid leukaemias and other cancers.  R.M. Kershaw, K. Gaston and                             P-S. Jayaraman. Book Chapter: Myeloid Cells: Biology & Regulation, Role in Cancer Progression and Potential Implications for Therapy (Peer reviewed) 2013. Editors: Spencer A. Douglas Nova Publishers ISBN: 978-1-62948-046-6

Dasatinib inhibits leukaemic cell survival by decreasing PRH/HHex phosphorylation resulting in increased repression of VEGF signalling genes.  Noy PJ, Gaston KL and Jayaraman PS. Leukaemia Research  2012 36(11):1434-7.

Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to derepress VEGF signalling genes and promote cell survival. Noy P, Williams H, Sawasdichai A, Jayaraman PS., and Gaston K.  Nucleic Acids Research (IF 9.1) 2012 40:9008-20

The Proline-Rich homeodomain protein PRH/Hhex forms stable oligomers that are highly resistant to denaturation. Shukla A., Burton N., Jayaraman PS. and Gaston K.  Plos One  2012 7(4): e35984.

The Transcription Factor Encyclopedia. Dimas Yusuf, Stefanie L Butland, et al., Noy P.  and Jayaraman P.-S  (Haematopoietically expressed homeobox) Genome Biology 2012 13 (3):R24

PRH/Hhex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling.  Noy P, Williams H, Sawasdichai A, Gaston K, and Jayaraman PS. Mol. Cell Biol.  2010 30(9):2120-34

A previously unrecognized promoter of LMO2 forms part of a transcriptional regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic leukaemia patients. Oram SH, Thoms JA, Pridans C, Janes ME, Kinston SJ, Anand S, Landry JR, Lock RB, Jayaraman PS, Huntly BJ, Pimanda JE, and Göttgens B.  Oncogene.  2010 29(43):5796-808

DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers. Soufi A, Sawasdichai A, Shukla A, Noy P, Dafforn T, Smith C, Jayaraman PS, and Gaston K.  Nucleic Acids Research  2010 38(21):7513-25.

In situ subcellular fractionation of adherent and non-adherent mammalian cells.  Sawasdichai A, Chen HT, Abdul Hamid N, Jayaraman PS, and Gaston K.  J Vis Exp.  2010 Jul 23;(41).

Activation of Proteinase-Activated Receptor 2 Stimulates Soluble Vascular Endothelial Growth Factor Receptor 1 Release via Epidermal Growth Factor Receptor Transactivation in Endothelial Cells.  Al-Ani B, Hewett PW, Cudmore MJ, Fujisawa T, Saifeddine M, Williams H, Ramma W, Sissaoui S, Jayaraman PS, Ohba M, Ahmad S, Hollenberg MD, and Ahmed A. Hypertension   2010 55(3):689-97.