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Dr Soo-Hyun Kim

Reader in Biomedical Sciences
Principal Investigator, Group Leader, Course Director

Disorders of sexual development are one of the most common types of birth defects affecting 3% of the population. Infertility is a major public health issue affecting 15% of couples. A small network of hypothalamic neurones is responsible for the coordinated secretion of gonadotropin-releasing hormone (GnRH) and the downstream sex hormones from the pituitary and gonads.  Disruption of this HPG axis causes delayed puberty and infertility, known as congenital hypogonadotropic hypogonadism (CHH). Kallmann syndrome (KS) is a CHH accompanied by anosmia. CHH/KS are clinically and genetically heterogeneous diseases requiring lifelong treatment and management. Dr Kim's research focuses on the fundamental mechanisms of human development and reproduction using CHH/KS as a unique disease model.

Dr Kim contributes strongly to teaching as well as research.  She has taken leading educational roles, developing and leading various modules in BSc, MSc and MRes courses.

Dr Kim joined St George’s, University of London in 2009, as a group leader.

Prior to this, she was a Senior Research Fellow at UCL Medical School, University College London where she worked with Professor Bouloux at the Centre for Neuroendocrinology (2003-2008).

During her postdoctoral research (1997 - 2003) at Cancer Research UK London Research Institute at Lincoln’s Inn Fields (previously Imperial Cancer Research Fund), she worked with Dr Hartmut Land and then with Dr Gordon Peters to investigate oncogenic signal pathways and cell cycle regulation, in particular, the mechanisms by which the tumour suppressor ARF and p53 operate, and how the cell cycle inhibitor p16 contributes to cellular ageing and cancer such as melanoma.

Dr Kim received her PhD from Rutgers University, New Jersey Medical School (1997), under the supervision of Professor Harvey Ozer who discovered the DNA tumour virus SV40 T antigen that can transform normal cells into immortal cancer cells.

Dr Kim has been a reviewer for prestigious grant-awarding bodies and scientific journals. She has been invited to join the European Cooperation in Science and Technology (COST) GnRH Network, an international consortium of physicians/researchers from 28 countries (profile page), and the UK Cilia Network, a national network of researchers working on cilia (my profile page).

Dr Kim has been involved with several learned societies, including the British Society for Cell Biology, Anatomical Society, British Society for Neuroendocrinology, Society for Endocrinology, Genetics Society, Biochemical Society, and Endocrine Society (USA). She also participates in public engagement activities, working with several patient groups.

As an established investigator in the field of CHH/KS, Dr Kim has made several important discoveries by integrating in vitro, interspecies, and clinical data, leading to improved diagnosis and counselling for unexplained infertility and new therapies for neonatal disorders and cancer.

Association of anosmin-1 in brain tumours: Anosmin-1, an extracellular matrix protein, was the first to be identified as the underlying genetic defect for X-linked KS. Following the initial finding on the role of anosmin-1 in FGF signalling, regulating GnRH neuronal development (PMC2785620), Dr Kim reported the first evidence on an oncogenic activity of anosmin-1 via its interaction with integrin and the tumour microenvironment.  Her group developed a novel computational approach with an original algorithm to analyse the gene expression profiles in a large collection of clinical samples obtained from St. George’s Hospital and demonstrated an inappropriate expression of anosmin-1 associated with high-grade brain tumours (PMC3869950).

Linking of CHH/KS with ciliopathy and the Hedgehog (Hh) signalling pathway: Dr Kim's group generated two transgenic animal models (mouse, zebrafish) and showed the first evidence for WDR11 function in cilia trafficking, suggesting CHH/KS as a new category of ciliopathy. They also demonstrated the first evidence for direct regulation of GnRH expression by Hh signalling pathway mediated by WDR11, suggesting Hh agonist as a potential therapy for CHH/KS and other associated clinical manifestations such as obesity (PMC5797970).

Linking of CHH/KS with primary hypogonadism: Using embryo organ culture live imaging and novel co-culture experiments, her group identified a role of WDR11 in primordial germ cell (PGC) migration, demonstrating the mechanisms of primary gonadal defects in KS/CHH.  This is important because it can explain why some patients do not respond to the current therapies which are aimed at hypothalamic dysfunction.

Differential regulation of Hedgehog (Hh) signalling in germ cell development: Hh is a signalling molecule that plays a critically important role during embryonic development, adult tissue homeostasis and in the aetiology of cancer. Her recent studies on PGCs led to new insights into the understanding of Hh signal regulation by cell-surface co-receptors. They found that the essential co-receptors BOC, CDO and GAS1 differentially interact with the primary PTCH1/2 receptors in the somatic and germ cell components of the developing gonads. This was the first demonstration of a PTCH2/GAS1-specific pathway, initiating distinct downstream signalling in parallel to the canonical pathway. Since Hh is one of the central morphogens and a major therapeutic target, this work (PMC7181751) has a strong impact on both fundamental and translational biology.

Further research on the molecular basis of the disease and the diverse signal pathways involved will help provide better diagnosis, treatment and management of the patients, as well as more precise genetic screening and counselling for the families.

PEER-REVIEWED MANUSCRIPT PUBLICATIONS (*Corresponding author)

  1. Lee, Y. Kim, P. Ataliotis, H. Kim, D. Kim, D. Bennett, N. Brown, L. Layman & S. Kim* (2022) Loss of Kallmann syndrome-associated gene WDR11 disrupts primordial germ cell development by affecting canonical and non-canonical Hedgehog signalling. (under review) preprint available at bioRxiv 2020.09.06.284927) https://doi.org/10.1101/2020.09.06.284927
  2. Louden, A. Poch, H-G Kim, A. Ben-Mahmoud, S-H. Kim & L. Layman (2021) Genetics of Hypogonadotropic Hypogonadism—Human and Mouse Genes, Inheritance, Oligogenicity and Genetic Counseling. Molecular & Cellular Endocrinology 534:111334-111352  doi: 10.1016/j.mce.2021.111334
  3. Kim & S. H. Kim* (2020) WD40-Repeat Proteins in Ciliopathies and Congenital Disorders of Endocrine System. Endocrinology & Metabolism 35(3):494-506.
  4. Kim, J. Lee, M. Seppala, M. Cobourne & S. H. Kim* (2020) Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. Nature Communications 11(1):1994. doi:10.1038/s41467-020-15897-3
  5. J. Kim, J. Y. Lee, M. Araki, K. Araki, T. Mohun, J. Känsäkoski, N. Brandstack, H. Kim, F. Miralles, C-H Kim, P. Ataliotis, N. A. Brown, H-G Kim, D. Osborn, J. P. Martinez-Barbera, T. Raivio, L. C. Layman, & S. H. Kim* (2018). WDR11‐mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome. EMBO Reports 19(2):269-289. doi: 10.15252/embr.201744632. In the top 20 most downloaded papers in 2018. Selected as the cover story & featured in the “Women in Science” by the publisher of all EMBO journals, Wiley.
  6. E. McCormack, D. Li, Y. J. Kim, J. Y. Lee, S. H. Kim, R. Rapaport, & M. A. Levine (2017). Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome. Journal of Clinical Endocrinology & Metabolism 102(7):2501-2507. doi: 10.1210/jc.2017-00332.
  7. COST Action BM1105, C. Badiu, M. Bonomi, I. Borshchevsky, M. Cools, M. Craen, C. Ghervan, M. Hauschild, E. Hershkovitz, E. Hrabovszky, A. Juul, H. Kim, P. Kumanov, B. Lecumberri, M. C. Lemos, V. Neocleous, M. Niedziela, S. P. Djurdjevic, L. Persani, F. Phan-Hug, D. Pignatelli, N. Pitteloud, V. Popovic, R. Quinton, N. Skordis, N. Smith, M. A. Stefanija, C. Xu, J. Young & A. A. Dwyer (2017). Developing and evaluating rare disease educational materials co-created by expert clinicians and patients: the paradigm of congenital hypogonadotropic hypogonadism. Orphanet Journal of Rare Diseases 12:57
  8. D. Quaynor, M. E. Bosley, C. G. Duckworth, K. R. Porter, S. H. Kim, H. Kim, L. P. Chorich, M. E. Sullivan, J. Choi, R. S. Cameron, & L. C. Layman (2016). Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome. Molecular and Cellular Endocrinology 437:86–96. doi:10.1016/j.mce.2016.08.007S.  Recommended in F1000Prime.
  9. Boehm, et al. (approved by S. H. Kim) (2015). European Consensus Statement on congenital hypogonadotropic hypogonadism - pathogenesis, diagnosis and treatment. Nat. Rev. Endocrinol. 11, 547–564 doi:10.1038/nrendo.2015.112
  10. Choy, H. Kim, D. Williams, D Palethorpe, G. Fellows, A. Wright, K. Laing, L. Bridges, F. Howe & S. Kim* (2013) Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways. Endocrine Related Cancer 21(1):85-99. In the top 10 most downloaded papers in 2014.
  11. P. Walker, R. C. Fowkes, F. Saleh, S. H. Kim, P. Wilkinson, V. Cabrera-Sharp, P. J. Talmud, S. E. Humphries, L. H. Looijenga, P. M. Bouloux. (2012) Genetic analysis of NR0B1 in congenital adrenal hypoplasia patients: Identification of a rare regulatory variant resulting in congenital adrenal hypoplasia and hypogonadal hypogonadism without testicular carcinoma in situ. Sexual Development 6(6):284–291
  12. T. Kim, J. H. So, S. H. Jung, D. G. Ahn, W. S. Koh, N. S. Kim, S. H. Kim, S. J. Lee & C. H. Kim (2011) Cug2 is essential for normal mitotic control and CNS development in zebrafish. BMC Developmental Biology 11:49
  13. Kim*, J. Turnbull & S. Guimond (2011) Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor Journal of Endocrinology 209(2): 139–151. (review manuscript, *corresponding author). In the top 10 most downloaded review papers during the first six months published, compared over 4 years. In the top 10 most cited articles in 2014. Total 1124 citations as of March 2022 (by Google Scholar).
  14. Xu, H. Kim, B. Bhagavath, S. Cho, J. Lee, K. Ha, I. Meliciani, W. Wenzel, R. Podolsky, L. Chorich, K. Stackhouse, A. Grove, L. Odom, M. Ozata, D. Bick, R. Sherins, S. Kim, R. Cameron & L. Layman (2011) Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome. Fertility and Sterility 95(5):1613-1620
  15. Kroll, S. Bolsover, S. Kim & P. Bouloux (2010) Kisspeptin-evoked calcium signals in isolated primary rat gonadotrophin-releasing hormone neurons. Neuroendocrinology 93:114-120
  16. G. Kim, J.W. Ahn, I. Kurth, R. Ullmann, H.T. Kim, A. Kulharya, K. Ha, Y. Itokawa, I. Meliciani, W. Wenzel, D. Lee, G. Rosenberger, M. Ozata, D. P. Bick, R. J. Sherins, T. Nagase, S. H. Kim, C. H. Kim, H.-H. Ropers, J. Gusella, V. Kalscheuer, C. Y. Choi & L. C. Layman. (2010) WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. American Journal of Human Genetics 87:465-479
  17. Choy & S. Kim* (2010) Biological actions and interactions of anosmin-1. Frontiers in Hormone Research Basel, Karger, vol 39, pp 78–93
  18. Hu, S. Guimond, P. Travers, S. Cadman, E. Hohenester, J. Turnbull, P. Bouloux* & S. Kim* (2009) Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1. Journal of Biological Chemistry 284:29905-29920 (*equal last author)
  19. Kim, Y. Hu, S. Cadman & P. Bouloux (2008) Diversity in FGFR1 signal regulation: learning from the investigation of Kallmann Syndrome. Journal of Neuroendocrinology 20:141-163
  20. Cadman, S. Kim, Y. Hu, D. Gonzalez-Martinez & P. Bouloux (2007) Molecular Pathogenesis of Kallmann’s Syndrome. Hormone Research 67:231-242
  21. Gonzalez, S. Kim, Y. Hu, S. Guimond, J. Schofield, G. Vannelli, J. Turnbull & P. Bouloux (2004) Anosmin-1 modulates FGFR1 signaling in human GnRH olfactoray neuroblasts through a heparan sulphate-dependent mechanism. Journal of Neuroscience 24:10384-10392
  22. Hu, D. Gonzalez, S. Kim & P. Bouloux (2004) Cross talk of anosmin-1, the protein implicated in X-linked Kallmann’s syndrome, with heparan sulphate and urokinase plasminogen activator Biochemical Journal 384:495-505
  23. Moulin, S. Llanos, S. Kim & G. Peters (2008) Binding to nucleophosmin determines the localization of human and chicken ARF but not its impact on p53. Oncogene 27: 2382–2389
  24. Kim, J. Rowe, H. Fujii, R. Jones, B. Schmierer, B. Kong, K. Kuchler, D. Foster, D. Ish-Horowicz & G. Peters (2006) Up-regulation of chicken p15INK4b at senescence and in the developing brain. Journal of Cell Science 119:2435-2443
  25. Kim, M. Mitchell, H. Fujii, S. Llanos & G. Peters (2003) Absence of p16INK4a and truncation of ARF tumor suppressors in chickens. Proceedings of National Academy of Science U.S.A. 100:211-216. Recommended in F1000Prime
  26. Perez-Roger, S. Kim, B. Griffiths, A. Sewing & H. Land (1999) Cyclins D1 and D2 mediate Myc-induced proliferation via sequestration of p27Kip1 and p21Cip1. EMBO J 18:5310-5320
  27. Kim*, S. Banga*, T. Dasgupta, K. Jha, P. Patsalis, R. Hauptschein, R. Dalla-Favera, P. Kraemer & H. Ozer (1997) SEN6, a locus for SV40-mediated immortalization of human cells, maps to 6q26-27. Oncogene 14:313-321 (*equal first author)
  28. Ozer, S. Banga, T. Dasgupta, J. Houghton, K. Hubbard, K. Jha, S. Kim, M. Lenahan, Z. Pang, J. Pardinas & P. Patsalis (1996) SV40-mediated immortalization of human fibroblasts. Experimental Gerontology 31:303-310

 BOOK CHAPTER PUBLICATION

  1. Hu, S. Kim, S. Cadman & P. Bouloux (2007) Insights into the molecular basis of Kallmann’s syndrome. Encycl Life Sci DOI : 10.1002/9780470015902.a0006100
  2. Kim, S. Banga, K. Jha & H. Ozer (1998) SV40-mediated transformation and immortalization of human cells. Simian Virus 40 : A Possible Human Polyomavirus. Brown F, Lewis AM (eds). Dev Biol Stand Basel, Karger, vol 94, pp297-302

Nov, 2019 - Oct, 2020: Global Educational Trust Fund. "Interdisciplinary collaboration for improved diagnosis and management of congenital disorders of neuroendocrine and reproductive disorders".

Jul, 2014 - Feb, 2018: Medical Research Council (MRC) Project Grant. "Dual functions of WDR11 in the pathogenesis of hypogonadotrophic hypogonadism."

Oct, 2012 – Mar, 2013: Wellcome Trust Institutional Strategic Support Fund, St George's, University of London Researcher Development Support Scheme. "The molecular mechanisms underlying Kallmann syndrome and normosmic hypogonadotrophic hypogonadism."

Jul, 2011- Jun, 2014: Enterprise Award, St George's, University of London, “Validation of diagnostic markers for brain tumours.”

Jul, 2010 – Jun, 2013: AIL-MAURI Academic Fund PhD Studentship Grant “Anosmin-1-mediated signalling events in neuronal differentiation and migration of human gonadotropin-releasing hormone neuroblasts.”

Jan, 2010 – Jun, 2010: Wellcome Trust Value In People Award - SGUL Human Resources Bridging Funding Scheme “Anosmin-1-mediated crosstalk between FGFR1 and TGF-beta signalling pathways.”

Jan, 2008 – Dec, 2010: Biotechnology & Biological Sciences Research Council Project Grant BB/F007167/1 “Extracellular modulation of multi-protein signalling complexes: molecular regulation of FGFR signalling by anosmin-1 & heparan sulphate proteoglycans”

Research Group

Yeon Joo Kim (Postdoctoral Research Fellow)

Bushra Mussa (Research Assistant)

 

PhD student: Katrina Brooks (third supervisor)

 

 Alumni

PhD students:

 

Ji Young Lee (primary supervisor)

Catherine Choy (primary supervisor)

 

Jaskaren Kohli (secondary supervisor)

Lorna FitzPatrick (secondary supervisor)

 

MRes/MSc students: 

Ntana Papadopoulou

Bushra Mussa

Vincent Umelue

Roina Nizami

Mosammat Raka Polyma

Sainab Melia Daghmoumi

Namakau Nakazwe

Sainab Melia Daghmoumi

Olivia Willets

Leah Esau

Janani Balasubramania Sarma

Jnina Eddous

Ester Paolocci

Elena Lin

Adam Mayar

Zahra Jamshidi Parvar

Adyam Naizghi

Shayalini Wignarajah

Rivkah Grant

Irene García Benítez

 

Collaborations:

 

Professor Lawrence Layman (Medical College of Georgia, Augusta University)

Dr Hyung Goo Kim (Qatar Biomedical Research Institute, Hamad Bin Khalifa University)

Professor Davide Calebiro (University of Birmingham)

Professor Eunjig Lee (Yonsei University)

Professor Timothy Mohun (Francis Crick Institute)

Dr Taneli Raivio (Helsinki University Central Hospital)

Dr Masatake Araki (Kumamoto University)

Dr Kim contributes strongly to teaching as well as research.

She obtained the Postgraduate Certificate in Healthcare and Biomedical Education (PGCert HBE) in 2012 and currently holds a Fellowship of Higher Education Academy.

She gives specialist lectures, tutorials and expert sessions and has been the module organiser for various courses in Biomedical Sciences and intercalated BSc programs. 

She supervises Research Projects for BSc, MRes, and MSc students. 

Dr Kim has been the lead for Reproduction and Development Pathway and is currently the Course Director for MRes Biomedical Sciences. 

She is a member of the Taught Postgraduate Course Committee and the Programmes Forum.

 

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