희귀유전질환심포지엄조직위원회
The Organizing Committee for Rare Genetic Diseases
PROFILE
이승복 교수
Bridging the Gap: From Diagnosis to Treatment in Rare Genetic Diseases
The reality is that rare diseases are very diverse in type and the number of patients for each disease is small, so only a very small number of diseases have available treatments. Above all, it is a very difficult clinical area from diagnosis to treatment, as more than half of cases are still difficult to diagnose clearly. Based on existing research, I would like to share my experience on how to proceed from actual patient diagnosis to expansion into related research.
서울대학교병원 소아청소년과
Education
2003.03 – 2009.02 M.D.Seoul National University, College of Medicine
2009.03 – 2014.02 Ph.D Seoul National University, Department of Biomedical Sciences
Major Publications
1. Identification of a novel IQCE variant in a Korean patient with nonsyndromic postaxial polydactyly. Clinical Dysmorphology 33 (3), 134-136 (2024)
2. Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study. Neurology: Genetics 10 (3), e200147 (2024)
3. B-Cell–Mediated Immunity Predicts Survival of Patients With Estrogen Receptor–Positive Breast Cancer. JCO Precision Oncology 8, e2300263 (2024)
4. Diagnostic uplift through the implementation of short tandem repeat analysis using exome sequencing. European Journal of Human Genetics, 1-4 (2024)
5. Broadening the scope of multigene panel analysis for adult epilepsy patients. Epilepsia Open (2024)
6. The transcriptomic landscape of caudal cell mass in different developmental stages of the chick embryo. Child's Nervous System 38 (11), 2101-2111 (2022)
7. Neurotoxicity of phenylalanine on human iPSC-derived cerebral organoids. Molecular Genetics and Metabolism (2022)
8. Short-term clinical outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy. Brain and Development 44 (4), 287-293 (2022)
9. TNNT1 myopathy with novel compound heterozygous mutations. Neuromuscular Disorders 32 (2), 176-184 (2022)
10. The extended clinical and genetic spectrum of CTNNB1-related neurodevelopmental disorder. Frontiers in Pediatrics (2022)
11. Whole genomic approach in mutation discovery of infantile spasms patients. Frontiers in neurology (2022)
12. Expanding the Clinical and Genetic Spectrum of Caveolinopathy in Korea. Ann Child Neurol 30 (3), 95-101 (2022)
13. Extended phenotypes of PIEZO1-related lymphatic dysplasia caused by two novel compound heterozygous variants. European Journal of Medical Genetics 64 (10), 104295 (2021)
14. A familial case of limb-girdle muscular dystrophy with CAV3 mutation. Journal of Genetic Medicine 16 (2), 67-70 (2019)
15. Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy. Experimental & molecular medicine 49 (5), e333-e333 (2017)
16. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS genetics 12 (8), e1006239 (2016)
17. Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type. Oncotarget 6 (19), 17764 (2015)
18. Genomic diagnosis by whole genome sequencing in a Korean family with atypical progeroid syndrome The Journal of Dermatology 42 (12), 1149-1152 (2015)
19. A family-based association study after genome-wide linkage analysis identified two genetic loci for renal function in a Mongolian population. Kidney international 83 (2), 285-292 (2013)
20. Molecular diagnosis of congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan using next-generation sequencing technology. Neuromuscular Disorders 23 (4), 337-344 (2013)
21. Targeted resequencing of candidate genes reveals novel variants associated with severe Behçet’s uveitis. Experimental & molecular medicine 45 (10), e49-e49 (2013)
22. Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis. PLoS One 8 (1), e53613 (2013)
23. Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population. Journal of medical genetics 49 (12), 747-752 (2012)
24. Copy Number Variation of Age-Related Macular Degeneration Relevant Genes in the Korean Population. PloS one 7 (2), e31243 (2012)
25. Genetic diagnosis of Duchenne and Becker muscular dystrophy using next-generation sequencing technology: comprehensive mutational search in a single platform. Journal of medical genetics 48 (11), 731-736 (2011)
임정화 박사
In vivo Gene Therapy for Hereditary Spastic Paraplegia
We have verified the novel function of ARL6IP1, a causative gene of the rare disease HSP, in maintaining MAM stability. We elucidated the pathogenic mechanism by revealing that ARL6IP1 mutations lead to motor neuron cell death and neuroinflammation. Using an Arl6ip1 knockout mouse model, we demonstrated the potential of AAV-based ARL6IP1 gene therapy to alleviate HSP symptoms and restore pathological changes
한국생명공학연구원
Education
2000-03 ~ 2004-02 BS., Dept. of Microbiology, Chungbuk National University
2005-03 ~ 2007-02 MS., Dept. of Biomedical Engineering and Biotechnology, Chungbuk National University
2009-03 ~ 2012-08 Ph.D., Dept. of Microbiology, Chungbuk National University
Professional Career
2012.10.15~present Stem Cell Convergenece Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Publication
1 Lim JH, Kang HM, Jung HR, Kim DS, Noh KH, Chang TK, Kim BJ, Sung DH, Cho HS, Chung KS, Kim NS, Jung CR. "Missense mutation of SPAST protein (I344K) results in loss of ATPase activity and prolonged the half-life, implicated in autosomal dominant hereditary spastic paraplegia." BBA-Molecular Basis of Disease (2018) 1864.10: 3221-3233.
2 Noh KH, Kang HM, Yoo W, Min Y, Kim D, Kim M, Wang S, Lim JH*, Jung CR*. "Ubiquitination of PPAR-gamma by pVHL inhibits ACLY expression and lipid metabolism, is implicated in tumor progression." Metabolism (2020) 110: 154302.
3 Noh KH, Kang HM, Oh SJ, Lee JY, Kim DH, Kim M, Chung KS, Son MY, Kim DS, Cho HS, Lee J, Lee DG, Lim JH*, Jung CR*. "A new experimental model to study human drug responses." Biofabrication (2020) 12.4: 045029.
4 Lim JH, Kim DH, Noh KH, Jung CR, Kang HM. "The proliferative and multipotent epidermal progenitor cells for human skin reconstruction in vitro and in vivo." Cell Proliferation (2022) 55.9: e13284.
5 Kang HM, Kim DH, Kim M, Min Y, Jeong B, Noh KH, Lee DY, Cho HS, Kim NS, Jung CR*, Lim JH*. "FBXL17/spastin axis as a novel therapeutic target of hereditary spastic paraplegia." Cell & Bioscience (2022) 12.1: 110.
6 Lim JH, Kang HM, Kim DH, Jeong B, Lee DY, Lee J, Baek JY, Cho HS, Son MY, Kim DS, Kim NS, Jung CR. “ARL6IP1 gene delivery rescues neurodegenerative pathology in a hereditary spastic paraplegia model by reducing neuroinflammation” Journal of Experimental Medicine (2023): e20230367.
Education
▪ Sep. 2022 – present Post-Doctoral Researcher, Pusan National University.
▪ Sep. 2016 – Aug. 2022 Ph.D., Department of Integrated Biological Science, Pusan National University.
▪ Mar. 2013 – Aug. 2016 B.S., Department of Molecular Biology, Pusan National University.
Research Experiences
김배훈 이사/연구소장
Avenues from target selection to clinical development of a novel drug candidate, PRG-N-01, on NF2-related Schwannomatosis (NF2-SWN)
This presentation summarizes the developmental process from molecular target selection to clinical trial of a first-in class drug candidate, PRG-N-01, on NF2-related schwannomatosis.
(주)피알지에스앤텍
Career
Korea University Ph.D 2000 ~ 2004.8 Molecular biology/ Microbiology
Biotechnology Institute in Korea University Research Assistant Professor 2004.9 ~2005.8 Biochemistry/Microbiology
Yale University Post-Doctoral Associate 2005.7 ~ 2010.6 Bacterial infection/Cell Autonomous Immunity/Cell Biology
Yale University Associate Research Scientist 2010.7 ~ 2015.9 Infection and Immunity/Microbiology/Cell Biology/ Inflamasome
Howard Hughes Medical Institute in Yale University Research Specialist 2015.10 ~ 2021.2 Viral Infection and Immunity/
Pyroptotic cell death/ Protein and Molecule interaction
PRG S & TRare Disease Research Center Research Director 2021.3 ~ present Rare Diseases
(HGPS/ALS/CMT1A/NF2 syndrome/Ewing Sarcoma/PMD)
Department of Molecular Biology Pusan University Adjunct Professor 2021.3 ~ 2023.2 & 2023.9 ~ present
Rare Diseases
(HGPS/ALS/CMT1A/NF2 syndrome/Ewing Sarcoma/PMD)
Publications
33. Kim BH, Chung YH, Woo TG, Kang Sm, Park S, Kim M, Park B-J. NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues. International Journal of Molecular Sciences. 2024 25(12):6558.
32. Zhu S*, Bradfield CJ*, Mamińska A*, Park ES*, Kim BH*, Kumar P, Huang S, Kim MJ, Zhang Y, Bewersdorf J, MacMicking JD (2024) “Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection” Science 383(6686):eabm9903
(* equal contribution)
31. Kim BH, Chung YH, Woo TG, Kang SM, Park S, Park BJ. (2023) “Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS.” Cells 12(18):2299
30. Kang SM, Seo S, Song EJ, Kweon O, Jo AH, Park S, Woo TG, Kim BH, Oh GT, Park BJ. (2023) “Progerinin, an Inhibitor of Progerin, Alleviates Cardiac Abnormalities in a Model Mouse of Hutchinson-Gilford Progeria Syndrome.” Cells 12(9):1232
29. Kim BH, Woo TG, Kang SM, Park S, Park BJ. (2022) “Splicing Variants, Protein-Protein Interactions, and Drug Targeting in Hutchinson-Gilford Progeria Syndrome and Small Cell Lung Cancer.” Genes (Basel) 2022 13(2):165
28. Cho JH, Park S, Kim S, Kang SM, Woo TG, Yoon MH, Lee H, Jeong M, Park YH, Kim H, Han YT, Suh YG, Kim BH, Kwon Y, Yun HW# and Park BJ# (2022) “RKIP induction promotes tumor-differentiation via SOX2 reduction in NF2 deficient conditions” Molecular Cancer Research 20(3):412-424
27. Woo TG, Yoon MH, Kang SM, Park S, Cho JH, Hwang YJ, Ahn J, Jang H, Shin YJ, Jung EM, Ha NC, Kim BH, Kwon Y, Park BJ (2021) “Novel chemical inhibitor against SOD1 misfolding and aggregation protects neuron-loss and ameliorates disease symptoms in ALS mouse model.” Communications Biology 4(1):1397
26. Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, Mamiñska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD (2021) “A human apolipoprotein L with detergent-like activity kills intracellular pathogens.” Science 373(6552):eabf8113
25. Wandel MP, Kim BH, Park ES, Boyle KB, Nayak K, Lagrange B, Herod A, Henry T, Zilbauer M, Rohde J, MacMicking JD, Randow F (2020) “Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms” Nature Immunology 21(8):880-891
* Highlighted in Nature Immunology New & Views
https://www.nature.com/articles/s41590-020-0727-0
24. Matta SK, Patten K, Wang Q, Kim BH, MacMicking JD, Sibley LD (2018) “NADPH oxidase and guanylate binding protein 5 restrict survival of avirulent type III strains of Toxoplasma gondii in naive macrophages” MBio 9(4):e01393-18
23. Bist P, Cheong WS, Ng A, Dikshit N, Kim BH, Pulloor NK, Khameneh HJ, Hedl M, Shenoy AR, Balamuralidhar V, Malik NBA, Hong M, Neutzner A, Chin KC, Kobayashi KS, Bertoletti A, Mortellaro A, Abraham C, MacMicking JD, Xavier RJ, Sukumaran B (2017) "E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP” Nature Communications 8:15865.
22. Kim BH, Chee JD, Bradfield CJ, Park ES, Kumar P, MacMicking JD (2016) “Interferon-induced guanylate-binding proteins in inflammasome activation and host defense.” Nature Immunology 17(5): 481-9
21. Kim JS*, Kim BH*, Jang JI, Eom JS, Kim HG, Bang IS, Park YK (* equal contribution) (2014) “Functional insights into tetratricopeptide repeat-like motifs of type III secretion chaperone SicA in Salmonella enterica serovar Typhimurium” FEMS Microbiology Letters 350(2):146-153
(* equal contribution)
20. Eom JS, Kim JS, Jang JI, Kim BH, Yoo SY, Choi JH, Bang IS, Lee IS, Park YK (2013) "Enhancement of Host Immune Responses by Oral Vaccination to Salmonella enterica Serovar Typhimurium harboring both FliC and FljB Flagella". PLoS One 8(9):e74850
19. Das R, Koo MS, Kim BH, Jacob ST, Subbian S, Yao J, Leng L, Levy R, Murchison C, Burman WJ, Moore C, Scheld WM, Kaplan G, MacMicking JD, Bucala R. (2013) “MIF is a critical mediator of the innate immune response to Mycobacterium tuberculosis.” PNAS 110(32):E2997-3006
* Highlighted in Yale News (July 22, 2013)
http://news.yale.edu/2013/07/22/understanding-global-epidemic-why-africans-hiv-are-more-susceptible-tb
18. Lee YH*, Kim S*, Helmann JD, Kim BH and Park YK. (2013) “RaoN, a Small RNA Encoded within Salmonella Pathogenicity Island-11, Confers Resistance to Macrophage-Induced Stress.” Microbiology-SGM 159 (Pt7):1366–1378
17. Kim JS*, Jang JI*, Eom JS, Kim HG, Kim BH, Bang IS, Bang SH and Park YK. (2013) “Molecular characterization of InvE regulator in the secretion of type III secretion translocases in Salmonella enterica serovar Typhimurium.” Microbiology-SGM 159 (Pt 3):446-61
16. Kim BH, Shenoy AR, Kumar P, Bradfield CJ and MacMicking JD. (2012) “IFN-inducible GTPases in host cell defense” Cell Host & Microbe (Review) 12(4):432-444
15. Jang JI, Kim JS, Eom JS, Kim HG, Kim BH, Lim S, Bang IS, Park YK. (2012) “Expression and delivery of tetanus toxin fragment C fused to the N-terminal domain of SipB enhances specific immune responses in mice.” Microbiology and Immunology 56:595–604
14. Matsuzawa T #, Kim BH, Shenoy AR, Kamitani S, Miyake M, and MacMicking JD. (2012) “IFN-gamma activates autophagy via the p38 MAPK signaling pathway.” Journal of Immunology 189:813-818 (# corresponding author)
* Highlighted in “IN THIS ISSUE” of Journal of Immunology
http://www.jimmunol.org/content/189/2/497.full
13. Bradfield CJ, Kim BH and MacMicking JD. (2012) “Crossing the Rubicon: New roads lead to host defense.” Cell Host & Microbe (Preview) 11(3): 221- 223
12. Marquis JF, Kapoustina O, Langlais D, Ruddy R, Dufour CR, Kim BH, MacMicking JD, Giguère V and Gros P. (2011) “Interferon regulatory factor 8 regulates pathways for antigen processing and presentation in myeloid cells.” Plos Genetics 7(6): e1002097
11. Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S and MacMicking JD. (2011) “A Family of IFN-γ-inducible 65kDa GTPases protect against bacterial infection.” Science 332(6030):717-721.
* Highlight in Nature Reviews Immunology 11, 372-373 (June 2011)
http://www.nature.com/nri/journal/v11/n6/full/nri3003.html
* Editor’s choice in Science Signaling, 4 (172), p.ec135 (May2011)
http://stke.sciencemag.org/cgi/content/abstract/sigtrans;4/172/ec135
* This paper is ranked in Faculty of 1000.
http://f1000.com/13355971
* Highly cited paper in BRIC
http://bric.postech.ac.kr/myboard/read.php?Board=hbs_treatise&id=25867&idauthorid=17345&ttype=1&ksr=1&FindText=김배훈
10. Shenoy AR, Kim BH, Choi HP, Matsuzawa T, Tiwari S, MacMicking JD. (2008) “Emerging themes in IFN--induced macrophage immunity by the p47 and p65 GTPase families.” Immunobiology 212 (9-10):771-784.
9. Kim HG*, Kim BH*, Kim JS, Eom JS, Bang IS, Bang SH, Lee IS, Park YK. (2008) “N-terminal residues of SipB are required for its surface localization on Salmonella enterica serovar Typhimurium.” Microbiology-SGM 154:207-216. (* equal contribution)
8. Kim BH*, Kim HG*, Kim JS, Jang IJ, and Park YK (2007) “Analysis of functional domains present in the N-terminus of the SipB protein.” Microbiology-SGM 153:2998-3008. (* equal contribution)
7. Lee YH, Kim BH, Kim JH, Yoon WS, Bang SH, Park YK. (2007) “CadC has a global translational effect during acid adaptation in Salmonella enterica serovar Typhimurium.” Journal of Bacteriology 189(6):2417-2425.
6. Kim BH, Kim S, Kim HG, Lee J, Lee IS, Park YK. (2005) “The formation of cyclopropane fatty acids in Salmonella enterica serovar Typhimurium.” Microbiology-SGM 151, 209-218
5. Kim BH, Bae GI, Bang IS, Bang SH, Choi JH, Park YK. (2004) “Expression of cspH gene upon nutrient up-shift in Salmonella enterica serovar Typhimurium.” Archives of Microbiology 182, 37-43.
4. Lee SY, Song MS, You KM, Kim BH, Bang SH, Lee IS, Kim CK, Park YK. (2002) “Monitoring 4-Chlorobiphenyl-degrading bacteria in soil microcosms by competitive quantitative PCR.” Journal of Microbiology 40, 274-281.
3. Kim BH, Lee HJ, Bang SH, Kim J, Park YK. (2001) “Cloning and sequencing analysis of cadC encoding transcriptional activator CadC from Salmonella typhimurium.” Journal of Microbiology 39,109-115.
2. Kim BH, Bang IS, Lee SY, Hong SK, Bang SH, Lee IS, Park YK. (2001) “Expression of cspH, encoding the cold shock protein in Salmonella enterica serovar Typhimurium UK-1.” Journal of Bacteriology 183, 5580-5588
1. Bang IS, Kim BH, Foster JW, Park YK. (2000) “OmpR regulates the stationary phase acid tolerance response of Salmonellar enterica serovar Typhimurium.” Journal of Bacteriology 182, 2245-2252
Recent Invited Talks
“Mutation-derived neo-protein-protein interactions as druggable target sites in various diseases
: A noble treatment for NF2 syndrome” 2023.10.26 Kyushu University (Fukuoka, Japan), 26th BOMUN Symposium
“Mutation-derived neo-protein-protein interactions as druggable target sites in various diseases”
2022. 10.25 (Busan, Korea), 3rd Symposium of Rare Genetic Diseases
“Update on progress in development program for Progerinin, an inhibitor of progerin” 2022.11.03 Royal Sonesta Hotel (Cambridge, MA, USA), The Progeria Research Foundation 11th International Scientific Workshop
“Cellular Innate Immunity and Inflammasome” 2021.10.08 GENOME OPINION, Inc, (Seongdong-gu, Seoul)
남기연 대표이사
Adrixetinib (Q702), a new potential treatment option for Edheim-Chester Disease (ECD)
Edheim Chester Disease is a rare blood cancer that occurs when macrophages in the tissue proliferate abnormally, affecting various tissues such as bones, lungs, and the central nervous system. We introduce the development of Adrixetinib (Q702) targeting patients with activating mutations in CSF1R among the driver genetic mutations of ECD.
(주)큐리언트
Education
Graduated from Unnam High School in Seoul in 1990
1995 Korea University, Biology, Bachelor's degree
1997 Korea University, Biology, Master's degree (Microbiology)
2003 Rutgers Medical School, New Jersey, Ph.D. in Computational Chemistry
2008 New York University, MBA (NYU Stern School of Business), Returned to Korea to establish Curient while attending school (Entrepreneurship, Finance)
Career
1997-1999 Researcher, Rutgers University, New Jersey
1999-2003 Researcher, Novartis Research Institute, USA
2003-2008 Senior Researcher and Project Manager, Merck Research Institute, USA
2008- Present CSO (Chief Scientific Officer) and CEO (Chief Executive Officer), Qurient Inc.