Medicine

Surinder Sahota

BSc (Hons), PhD

Primary position:
Reader in Immunogenetics

Background

The University of Southampton

Dr Sahota was appointed as Reader in 2006. He graduated in Biochemistry and obtained his PhD in Microbial Biochemistry from the University of London, UK followed by an appointment as Lecturer and Post-doctoral Scholar in Microbial Genetics at the University of California Los Angeles, USA. Following his return to the UK, Dr Sahota engaged different research interests, and undertook cancer research at St. George’s Hospital Medical School and the Charing Cross & Westminster Hospital Medical School, University of London (examining steroid receptors in breast cancer). He was subsequently appointed in 1992 as Research Fellow / Senior Research Fellow / LRF Senior Scientist in the Cancer Sciences Division, School of Medicine, University of Southampton, before his current Faculty position.

Much of the earlier research work in Cancer Sciences, Southampton focused on developing immunogenetics to profile pathogenesis and progression in B-lymphocyte malignancy, with a special focus on multiple myeloma, a plasma cell tumour. More recent work has utilised genome wide whole exome sequencing to examine mutations to define B-cell tumour origins and behaviour, seeking to link genomic mutations with functional outcomes. Dr Sahota’s group is also interested in defining tumour-associated antigens, and in targeted immunotherapy using DNA vaccine designs. His group comprises post-doctoral scientists, visiting fellows, PhD students (non-clinical and clinical), and 4th year medical undergraduates. The group is based within the Faculty of Medicine.

Qualifications

BSc (Hons), Biochemistry, University of London 1977
PhD, University of London 1984

Appointments held

Postdoctoral Scholar and Lecturer, Department of Microbiology, University of California Los Angeles, USA

Postdoctoral Fellow, Department of Clinical Biochemistry, St. George’s Hospital Medical School / Department of Medical Oncology, Charing Cross & Westminster Hospital Medical School, University of London

Postdoctoral Fellow / Senior Research Fellow / LRF Senior Scientist, Cancer Sciences Division, School of Medicine, University of Southampton

Reader, Faculty of Medicine, University of Southampton 2006 –

Dr Surinder Sahota's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Weston-Bell, N., Gibson, J., John, M., Ennis, S., Pfeifer, S., Cezard, T., Ludwig, H., Collins, Andrew, Zojer, N. and Sahota, S. S. (2013) Exome sequencing in tracking clonal evolution in multiple myeloma following therapy. Leukemia, 27, (5), 1188-1191. (doi:10.1038/leu.2012.287). (PMID:23147253).
Weston-Bell, N.J., Hendriks, D., Sugiyarto, G., Bos, N.A., Kluin-Nelemans, H.C., Forconi, F. and Sahota, S.S. (2013) Hairy cell leukemia cell lines expressing annexin A1 and displaying B-cell receptor signals characteristic of primary tumor cells lack the signature BRAF mutation to reveal unrepresentative origins. Leukemia, 27, 241-245. (doi:10.1038/leu.2012.163). (PMID:22705994).
van Duin, Mark, Broyl, Annemiek, de Knegt, Yvonne, Goldschmidt, Hartmut, Richardson, Paul G, Hop, Wim C J, van der Holt, Bronno, Joseph-Pietras, Debora, Mulligan, George, Neuwirth, Rachel, Sahota, Surinder S. and Sonneveld, Pieter (2011) Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy. Haematologica, 96, (11), 1662-1669. (doi:10.3324/haematol.2010.037978). (PMID:21791470).
van Duin, Mark, Broyl, Annemiek, de Knegt, Yvonne, Goldschmidt, Hartmut, Richardson, Paul G., Hop, Wim C.J., van der Holt, Bronno, Joseph-Pietras, Debora, Mulligan, George, Neuwirth, Rachel, Sahota, Surinder S. and Sonneveld, Pieter (2011) Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy. Haematologica, 96, (11), 1662-1669. (doi:10.3324/haematol.2010.037978). (PMID:21791470).
Pfeifer, Sabine, Perez-Andres, Martin, Ludwig, Heinz, Sahota , Surinder S. and Zojer, Niklas (2011) Evaluating the clonal hierarchy in light-chain multiple myeloma: implications against the myeloma stem cell hypothesis. Leukemia, 25, 1213-1216. (doi:10.1038/leu.2011.70). (PMID:21494259).
Sozzi, Elisa, Amato, Teresa, Sahota, Surinder S., Nuti, Sandra, Raspadori, Donatella, Sicuranza, Anna, Cencini, Emanuele, Tosi, Piero, Lauria, Francesco and Forconi, Francesco (2011) Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia. Hematological Oncology, 29, (1), 31-37. (doi:10.1002/hon.952). (PMID:20658474).
Joseph-Pietras, D., Gao, Y., Zojer, N., Ait-Tahar, K., Banham, A.H., Pulford, K., Rice, J., Savelyeva, N. and Sahota, S.S. (2010) DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma. Leukemia, 24, (11), 1951-1959. (doi:10.1038/leu.2010.196). (PMID:20861911).
Sahota, Surinder S., Babbage, Gavin and Weston-Bell, Nicola J. (2009) CD27 in defining memory B-cell origins in Waldenstrom’s macroglobulinemia. Clinical Lymphoma, Myeloma & Leukemia, 9, (1), 33-35. (doi:10.3816/CLM.2009.n.007).
Sahota, Surinder S., Zojer, N, Babbage, Gavin, Joseph Pietras, Debora , Weston-Bell, Nicola J., vanderkerken, K, Sonneveld, P, Klein, B, Pulford, K, Rice, J., Savelyeva, Natalia and Ottensmeier, C.H. (2009) Defining Multiple Myeloma as a target for DNA fusion gene vaccines. Clinical Lymphoma and Myeloma, 9 (Suppl 2), (S23)
Forconi, Francesco, Sozzi, Elisa, Rossi, Davide, Sahota, Surinder S., Amato, Teresa, Raspadori, Donatella, Trentin, Livio, Leoncini, Lorenzo and Gaidano, Gianluca (2008) Selective influences in the espresse immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia. Haematologica, 93, (5), 697-705. (doi:10.3324/haematol.12282). (PMID:18387977).
Forconi, Francesco, Sozzi, Elisa, Rossi, Davide, Sahota, Surinder S, Amato, Teresa, Raspadori, Donatella, Trentin, Livio, Leoncini, Lorenzo, Gaidano, Gianluca and Lauria, Francesco (2008) Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia. Haematologica, 93, (5), 697-705. (doi:10.3324/haematol.12282). (PMID:18387977).
Weston-Bell, Nicola J., Townsend, Mark R., Forconi, Francesco, Stevenson, Freda K and Sahota, Surinder S. (2007) IgM(+) B-cells lacking CD27 expression display somatically mutated Ig V-H genes and define a new memory population. Blood (ASH Annual Meeting Abstracts), 110, (11), 774A-774A.
Stevenson, F.K., Campos-Perez, J., Sahota, S. and Ottensmeier, C. (2007) DNA vaccines to suppress myeloma. Haematologica-the Hematology Journal, 92, (6, supplement 2), 45-46.
Zojer, N., Schreder, M., Graffi, S., Fuchs, D., Sahota, S. and Ludwig, H. (2007) Indoleamine 2,3-dioxygenase (IDO) may not be a major factor for tumor immune evasion in multiple myeloma. Haematologica-the Hematology Journal, 92, (Supp/2), PO-241.
Sahota, S.S., Babbage, G., Townsend, M., Weston-Bell, N.J. and Stevenson, F.K. (2007) Tracking the malignant cell of origin in Waldenstrom's macroglobulinemia. Haematologica-the Hematology Journal, 92, (6, supplement 2), 78-79.
Babbage, G., Townsend, M., Zojer, N., Mockridge, I.C., Garand, R., Barlogie, B., Shaughnessy, J., Stevenson, F.K. and Sahota, S.S. (2007) Letter to the Editor. IgM-expressing Waldenstrom's macroglobulinemia tumor cells reveal a potential for isotype switch events in vivo. Leukemia, 21, (4), 827-830. (doi:10.1038/sj.leu.2404538).
Sahota, S.S., Bazhin, A., Goonewardena, M., Zojer, N., Schadendorf, D., Stevenson, F.K. and Eichmuller, S. (2007) cTAGE are potential multiple myeloma associated antigens [In: Cancer immunotherapy 2006 meets strategies for immune therapy p.414]. Cancer Immunology Immunotherapy, 56, (3), 403-427. (doi:10.1007/s00262-006-0201-3).
Sahota, Surinder S., Goonewardena, C. Madusha, Cooper, Christopher D.O., Liggins, Amanda P., Ait-Tahar, Kamal, Zojer, Niklas, Stevenson, Freda K., Banham, Alison H. and Pulford, Karen (2006) Correspondence to the editor: PASD1 is a potential multiple myeloma-associated antigen. Blood, 108, (12), 3953-3955.
Jardin, F., Sahota, S. S., Ruminy, P., Parmentier, F., Picquenot, J. M., Rainville, V., Buchonnet, G., Leprêtre, S., Tilly, H. and Bastard, C. (2006) Novel Ig V gene features of t(14;18) and t(3;14) de novo diffuse large B-cell lymphoma displaying germinal center-B cell like and non-germinal center-B cell like markers. Leukemia, 20, (11), 2070-2074. (doi:10.1038/sj.leu.2404370).
Sahota, Surinder Singh and Stevenson, Freda K. (2006) Lineage complexity in multiple myeloma? Leukemia & Lymphoma, 47, (9), 1997-1998. (doi:10.1080/10428190600758686).
Eurelings, Marijke, Notermans, Nicolette C., Lokhorst, Henk M., van Kessel, Berris, Jacobs, Bart C., Wokke, John H.J., Sahota, Surinder S. and Bloem, Andries C. (2006) Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy. Journal of Neuroimmunology, 175, (1-2), 152-159. (doi:10.1016/j.jneuroim.2006.02.008 ).
Babbage, Gavin, Ottensmeier, Christian H., Blaydes, Jeremy, Stevenson, Freda K. and Sahota, Surinder S. (2006) Immunoglobulin heavy chain locus events and expression of activation-induced cytidine deaminase in epithelial breast cancer cell lines. Cancer Research, 66, (8), 3996-4000. (doi:10.1158/0008-5472.CAN-05-3704).
Sahota, Surinder S., Babbage, Gavin, Townsend, Mark, Mockridge, Ian C., Zojer, Niklas, Garand, Richard, Shaughnessy, John and Stevenson, Freda K. (2005) IgM-expressing Waldenstrom's Macroglobulinemia tumor cells reveal a potential for isotype switch. Blood, 106, (11), p.292A.
Jardin, Fabrice and Sahota, Surinder S. (2005) Targeted somatic mutation of the BCL6 proto-oncogene and its impact on lymphomagenesis. Hematology, 10, (2), 115-129. (doi:10.1080/10245330400026105).
Konduri, K., Sahota, S.S., Babbage, G., Tong, A.W., Kumar, P., Newman, J.T. and Stone, M.J. (2005) Immunoglobulin M myeloma: evaluation of molecular features and cytokine expression. Clinical Lymphoma, 5, (4), 285-289.
Sahota , Surinder S., Babbage , Gavin, Garand, Richard, Zojer, Niklas and Stevenson , Freda (2005) Dynamics of activation induced cytidine deaminase expression in t(11;14) mantle cell lymphoma. Blood, 105, (7), 2997-2999.
Forconi, Francesco, Sahota, S.S., Lauria, . and Stevenson, F.K. (2004) Revisiting the definition of somatic mutational status in B-cell tumors: does 98% homology mean that a V(H)-gene is unmutated? Leukemia, 18, (4), 882-883. (doi:10.1038/sj.leu.2403312). (PMID:14973503).
Forconi, Francesco, Sahota, Surinder S., Raspadori, Donatella, Ippoliti, Micaela, Babbage, Gavin, Lauria, Francesco and Stevenson, Freda K. (2004) Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch. Blood, 104, (10), 3312-3317. (doi:10.1182/blood-2004-03-0950).
Babbage, Gavin, Garand, Richard, Robillard, Nelly, Zojer, Niklas, Stevenson, Freda K. and Sahota, Surinder S. (2004) Mantle cell lymphoma with t(11;14) and unmutated or mutated VH genes expresses AID and undergoes isotype switch events. Blood, 103, (7), 2795-2798. (doi:10.1182/blood-2003-05-1632).
Orchard, Jenny, Garnd, Richard, Davis, Zadie, Babbage, Gavin, Sahota, Surinder, Matutes, Estella, Catovsky, Daniel, Thomas, Peter W., Avet-Loiseau, Hervé and Oscier, David (2003) A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease. Blood, 101, (12), 4975-4981. (doi:10.1182/blood-2002-06-1864).
Sahota, Surinder S., Forconi, Francesco, Ottensmeier, Christian H. and Stevenson, Freda K. (2003) Origins of the malignant clone in typical Waldenstrom's macroglobulinemia. Seminars in Oncology, 30, (2), 136-141. (doi:10.1053/sonc.2003.50072).
Zojer, Niklas, Ludwig, Heinz, Fiegl, Michael, Stevenson, Freda K. and Sahota, Surinder S. (2003) Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma. Blood, 101, (10), 4137-4139. (doi:10.1182/blood-2002-09-2825).
Jardin, Fabrice, Bastard, Christian, Contentin, Nathalie, Parmentier, Françoise, Picquenot, Jean-Michel, Tilly, Hervé, Stevenson, Freda K. and Sahota, Surinder S. (2003) Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma. Blood, 102, (5), 1872-1876. (doi:10.1182/blood-2002-12-3630).
Sahota, Surinder S., Forconi, Francesco, Ottensmeier, Christian H., Provan, Drew, Oscier, David G., Hamblin, Terry J. and Stevenson, Freda K. (2002) Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events. Blood, 100, (4), 1505-1507.
Forconi, Francesco, King, Catherine A., Sahota, Surinder S., Kennaway, Christopher K., Russell, Nigel H. and Stevenson, Freda K. (2002) Insight into the potential for DNA idiotypic fusion vaccines designed for patients by analysing xenogeneic anti-idiotypic antibody responses. Immunology, 107, (1), 39-45. (doi:10.1046/j.1365-2567.2002.01452.x).
Adams, S.P., Sahota, S.S., Mijovic, A., Czepulkowski, B., Padua, R.A., Mufti, G.J. and Guinn, B.A. (2002) Frequent expression of HAGE in presentation chronic myeloid leukaemias. Leukemia, 16, 2238-2242. (doi:10.1038/sj.leu.2402732).
Stevenson, Freda K., Sahota, Surinder S., Ottensmeier, Christian H., Zhu, Delin, Forconi, Francesco and Hamblin, Terry J. (2001) The occurrence and significance of V gene mutations in B cell-derived human malignancy. Advances in Cancer Research, 83, 81-116. (doi:10.1016/S0065-230X(01)83004-9).
Forconi, Francesco, Sahota, Surinder S., Raspadori, Donatella, Mockridge, Christopher I., Lauria, Francesco and Stevenson, Freda K. (2001) Tumor cells of hairy cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing. Blood, 98, (4), 1174-1181.
Sahota, S.S., Davis, Z., Hamblin, T. J. and Stevenson, F. K. (2000) Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia. Blood, 95, (11), 3534-3540.
Garand, R., Sahota, S.S., Avet-Loiseau, H., Talmant, P., Robillard, N., Moreau, A., Gaillard, F., Stevenson, F.K. and Bataille, R. (2000) IgG-secreting lymphoplasmacytoid leukaemia: a B-cell disorder with extensively mutated VH genes undergoing Ig isotype-switching frequently associated with trisomy 12. British Journal of Haematology, 109, (1), 71-80. (doi:10.1046/j.1365-2141.2000.01971.x).
Stevenson, F., Zhu, D., Spellerberg, M.B., Rice, J., King, C.A., Thompsett, A.R., Sahota, S.S. and Hamblin, T.J. (2000) DNA vaccination against cancer antigens. Ernst Schering Foundation Symposium Proceedings, (30), 119-36.
Stevenson, Freda K., Sahota, Surinder S., Zhu, D., Ottensmeier, Christian H., Chapman, C., Oscier, D.G. and Hamblin, T.J. (1998) Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes. Immunological Reviews, 89, (11), 4153-4160. (doi:10.1111/j.1600-065X.1998.tb01446.x). (PMID:9602369).

Book Section

McCann, Katy, Sahota, Surinder S., Stevenson, Freda K. and Ottensmeier, Christian H. (2005) Idiotype gene rescue in follicular lymphoma. In, Lymphoma: methods and protocols. , Humana Press, 145-171. (Methods in Molecular Medicine, 115).
Sahota, Surinder S., Townsend, Mark and Stevenson, Freda K. (2005) Identification and assembly of V genes as idiotype-specific DNA fusion vaccines in multiple myeloma. In, Multiple Myeloma: methods and protocols. , Humana Press, 105-120. (Methods in Molecular Medicine, 113).
Sahota, Surinder S., Babbage, Gavin, Zojer, Niklas, Ottensmeier, Christian H. and Stevenson, Freda K. (2005) Determining mutational status of immunoglobulin v genes in chronic lymphocytic leukemia: a useful prognostic indicator. In, Lymphoma: methods and protocols. , Humana Press, 129-144. (Methods in Molecular Medicine, 115).
Stevenson, Freda K., Zhu, Delin, Spellerberg, Myfanwy, King , Catherine A., Sahota , Surinder S., Rice, Jason, Thomsett , Andrew R. and Hamblin, Terry J. (2000) DNA Vaccines against B-cell tumors. In, Stern, Peter L., Beverley, Peter L.C. and Carroll, Miles W. (eds.) Cancer vaccines and immunotherapy. Cambridge, GB, Cambridge University Press, 218-236.
 

Research

Research Interests

Multiple myeloma – Pathogenesis, Progression and Targeted Therapy

The group has a particular focus on understanding the pathogenesis of multiple myeloma (MM), an incurable disease where malignant plasma cells accumulate in the bone marrow. One debilitating feature of the disease results from multiple osteolytic foci in the skeleton, induced by tumour growth. MM is often preceded by a proliferative condition termed monoclonal gammopathy of undetermined significance (MGUS), where a limited plasma cell expansion occurs, but it is as yet not clear what factors underlie transformation to full blown disease.

Plasma cells are terminally differentiated B-cells, but in MM, questions still remain regarding the maturation status of the cell giving rise to this tumour. We have been interested in utilizing immunoglobulin variable (V) region gene analysis to track disease evolution in B-cell tumours. V genes have also been shown to be useful, objective markers for disease classification and can predict clinical behaviour. Our group has been instrumental in defining key aspects of the pathogenesis and serial progression of MGUS to MM using this approach. On-going studies are aimed at understanding which molecular mechanisms may be contributing to malignant transformation and progression, including use of next generation sequencing to interrogate the tumour exome and genome. More recently, we were part of the European Myeloma Network specialist network ‘MSCNET’ investigating a role for a stem cell in MM evolution. Current collaborative work funded under the EU FP7 programme as part of ‘OVER-MyR’ is aimed at evaluating MM:niche cell interactions, especially in relation to mechanisms of drug resistance.

We are also interested in exploiting insights from pathogenesis of MM to inform targeted therapy, specifically by DNA vaccination. The detailed characterization on MM V genes allowed targeted DNA therapy against the tumour idiotype. Recent work has been directed at identifying antigens retained by malignant plasma cells following therapy, to allow effective vaccination against MM cells on relapse. We have focused on cancer testis antigens (CTAs) in this regard. Vaccines generated against newly identified CTAs in MM are also currently being evaluated using pre-clinical transgenic models.

There is a parallel interest in probing developmental events in the origins and behaviour of other B-cell tumours, in particular Hairy Cell Leukaemia (HCL) and Waldenstrom’s macroglobulinemia (WM). Here, our investigations include analysis of early and late maturation events, as revealed by analysis of somatic mutation imprints in Ig and non-Ig loci, especially the 5’ non-coding region of the BCL-6 gene, a proto-oncogene encoding a transcriptional repressor. In addition, we are evaluating the role of the B-cell receptor and niche interactions in HCL and WM persistence. In these B-cell tumours, notable observations have been established by PhD rotation project students and undergraduate medical students.

Individuals interested in joining any aspect of this research work are encouraged to contact the group informally. The group usually has one or two places for medical students undertaking a study in depth by research as part of the BMed / MMed Sci degrees.

Academic unit:  Cancer Sciences

Responsibilities

Postgraduate student supervision

2004 – present: PhD supervision (Principle / Co-Supervisor)

Faculty of Medicine

Postgraduate Research Programmes (PRS) Committee
PRS Student Progress Committee
Integrated PhD Programme Group

Cancer Sciences Academic Unit

CSD Management Committee
CRUK Centre Governance Board
CRUK Centre Executive Group

National responsibilities

Peer-review of journal articles for: Blood, Cancer Research, Leukemia, Haematologica, British Journal of Haematology, Leukemia Research, International Journal of Cancer, Immunology, PLoS One, American Journal of Pathology, FEBS Letters, BioMed Central (BMC Genomics), Genes, Chromosomes & Cancer; FASEB Journal, Journal of Leukocyte Biology, J Pathology, Clinical Lymphoma and Myeloma, Cancer Biology & Therapy, Cancer Biology & Therapy, Journal of Histochemistry & Cytochemistry

Peer-review of grant applications to: MRC, Leukaemia & Lymphoma Research Fund, Cancer Research UK, Kay Kendall Leukaemia Foundation, Breast Cancer Campaign, Yorkshire Cancer Research, Cancer Research Ireland, Association for International Cancer Research, Stichting tegen Kanker (Belgian Foundation Against Cancer), Fonds Wetenschappelijk (FWO) Research Foundation, Belgium, United States-Israel Binational Science Foundation, Israel, Israel Science Foundation, International Waldenstrom’s macroglobulinemia Foundation (USA), International Myeloma Foundation (USA), Multiple Myeloma Research Foundation (USA).

Advisory Board: 11th International Workshop on Multiple Myeloma and 4th International Workshop on Waldenstrom’s macroglobulinemia (2007)

Other Professional Activities:
Member European Myeloma Network (Workpackage Leader)
Member of UK Myeloma Forum
Member of UK Myeloma Forum Scientific Committee

Teaching Responsibilities


Cancer Sciences Academic Unit Staff Post-graduate Lead

Cancer Sciences Academic Unit Pastoral Advisor (for Postgraduates)

CRUK Centre. Training Lead (non-clinical)

BIOL3037 Immunology. Course Co-ordinator & Lecturer. Organise course curriculum and delivery to Year 3 undergraduates, taught at Highfield Campus

BIOL6038 Immunology. Course Co-ordinator & Tutor (Highfield Campus)

BIOL3043 Molecular and Cellular Pathology. Lecturer on Cancer Vaccines (Highfield Campus)

Course Facilitator BM4 Medicine (Year 1)

BM5 Year 2 Immunology. Lecturer on B-cell immunology

MMedSci. Course Tutor (research evaluation) / Invited Chair (‘Inspire’ programme)

4 Yr Integrated PhD Cancer Pathway. Co-ordinator Research Rotation Projects. Interview Panel (appointments & progress viva voce). Project Supervisor.

4th Year Study-in-depth medical undergraduates. Project Supervisor.

Contact

Dr Surinder Sahota
Phone: (023) 8120 8768
Fax: (023) 8120 1385
Email: s.s.sahota@soton.ac.uk

Room Number: SGH/CSB/MP891