Harvard Catalyst Profiles

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Yee-Ming Chan, M.D., Ph.D.


Yale University, New Haven, CTB.S.05/1993Biology
University of California, San Francisco, San Francisco, CAPh.D.12/2000Genetics
University of California, San Francisco, San Francisco, CAM.D.06/2002
University of California, San Francisco, San Francisco, CA06/2005Pediatrics (Internship and Residency)
Boston Children's Hospital, Boston, MA06/2008Pediatric Endocrinology (Clinical Fellowship)
Massachusetts General Hospital, Boston, MA06/2005Reproductive Endocrinology (Research Fellowship)
Robert P. Masland, Jr. Teaching Award
Elected Member, Society for Pediatric Research
Pediatric Endocrinology Fellowship Teaching Award

Available: 01/03/17, Expires: 12/30/22

What causes puberty to start? Why does it happen at different ages for different children? We are addressing these questions by studying children with delayed puberty using several approaches:

  1. Analysis of clinical data (captured in a research database) to define the clinical characteristics of children with delayed puberty and to identify potential phenotypic subgroups.
  2. In-person research visits with adults who had delayed puberty to study the long-term consequences of delayed puberty.
  3. Human genetic studies to identify both common and rare genetic variants that contribute to delayed puberty, with the broader goal of understanding how pubertal timing is determined in general.

The time commitment is flexible. Though listed as "6 months or more," students looking for a shorter project are welcome to contact our group.

Available: 01/01/20, Expires: 12/31/22

Differences of sex development (also called intersex conditions) are conditions in which an underlying hormonal issue results in atypical development of the genitals. We are conducting a study to identify genetic causes of DSD as well as to assess the impact of receiving genetic testing results on families.

Student role may include: analysis of genetic data, retrospective chart review focusing on a specific DSD condition, gaining experience in clinical research (e.g., assisting with recruitment, obtaining consent, and coordinating sample collection). The student will be expected to provide regular updates on progress, attend weekly group meeting (schedule permitting). Students of any level and any time availability are invited. Students should have familiarity with human genetics. For analysis of genetic data, programming skills will be helpful.

The project PI is typically will meet with student weekly or biweekly and will also be available by EMail, and other members of the research team will also be available for assistance.

Available: 01/01/20, Expires: 12/31/22

The Boston Children's Hospital Gender Multidisciplinary Service (GeMS) provides multiple services to transgender and gender-variant (TGD) youth, including hormonal treatments. Treatment with puberty blockers (GnRH analogs) can be used to halt the development of secondary sex characteristics that may be discordant with a patient's identified gender, and treatment with gender-affirming hormones (estradiol, testosterone) can be used to induce secondary sex characteristics concordant with identified gender. Boston Children's Hospital is part of a 4-site consortium (with Children's Hospital Los Angeles, University of California San Francisco, and Lurie Children's Hospital in Chicago) conducting a longitudinal study of physiological and psychosocial outcomes of these treatments.

Available: 01/03/17, Expires: 12/30/22

Delayed puberty is a common pediatric condition, but the causes and consequences of delayed puberty remain incompletely understood. This project uses three approaches to study delayed puberty: 1) A retrospective chart review to define the clinical characteristics of children with delayed puberty and to identify potential phenotypic subgroups. 2) In-person research visits with adults with a history of delayed puberty to study the long-term consequences of delayed puberty. 3) Human genetic studies to identify both common and rare genetic variants that can contribute to delayed puberty, with the broader goal of understanding how pubertal timing is determined in general. The time commitment is flexible. Though listed as "6 months or more," students looking for a shorter project are welcome to contact our group. There is potential for a "gap" year to be funded by the Doris Duke Charitable Foundation through their Clinical Research Mentorship. The application deadline for the 2017 cycle is January 24, 2017.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01HD090071 (CHAN, YEE-MING) Apr 11, 2017 - Mar 31, 2022
    Delayed Puberty: Causes and Consequences, Genotypes and Phenotypes
    Role: Principal Investigator
  2. R01HD089521 (HIRSCHHORN, JOEL N) Sep 10, 2016 - May 31, 2021
    Exome Sequencing in Disorders of Sex Development: Impact on Patients and Families
    Role: Co-Investigator
  3. R01HD082554 (OLSON-KENNEDY, JOHANNA L) Aug 1, 2015 - Jun 30, 2020
    The Impact of Early Medical Treatment in Transgender Youth
    Role: Co-Investigator
  4. R01HD074579 (MULLINS, LARRY L.) Jul 5, 2013 - Feb 28, 2023
    Long-Term Outcomes of Interventions for Reproductive Dysfunction
    Role: Co-Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Chan YM, Lippincott MF, Sales Barroso P, Alleyn C, Brodsky J, Granados H, Roberts SA, Sandler C, Srivatsa A, Seminara SB. Using Kisspeptin to Predict Pubertal Outcomes for Youth with Pubertal Delay. J Clin Endocrinol Metab. 2020 Mar 31. PMID: 32232399.
  2. Zhu J, Feldman HA, Eugster EA, Fechner PY, Nahata L, Thornton PS, Chan YM. PRACTICE VARIATION IN THE MANAGEMENT OF GIRLS AND BOYS WITH DELAYED PUBERTY. Endocr Pract. 2020 Mar; 26(3):267-284. PMID: 31859552.
  3. Lippincott MF, León S, Chan YM, Fergani C, Talbi R, Farooqi IS, Jones CM, Arlt W, Stewart SE, Cole TR, Terasawa E, Hall JE, Shaw ND, Navarro VM, Seminara SB. Hypothalamic Reproductive Endocrine Pulse Generator Activity Independent of Neurokinin B and Dynorphin Signaling. J Clin Endocrinol Metab. 2019 10 01; 104(10):4304-4318. PMID: 31132118.
  4. Chan YM, Feld A, Jonsdottir-Lewis E. Effects of the Timing of Sex-Steroid Exposure in Adolescence on Adult Health Outcomes. J Clin Endocrinol Metab. 2019 10 01; 104(10):4578-4586. PMID: 31194243.
  5. Millington K, Liu E, Chan YM. The Utility of Potassium Monitoring in Gender-Diverse Adolescents Taking Spironolactone. J Endocr Soc. 2019 May 01; 3(5):1031-1038. PMID: 31065620.
  6. Harris RM, Chan YM. Ethical issues with early genitoplasty in children with disorders of sex development. Curr Opin Endocrinol Diabetes Obes. 2019 02; 26(1):49-53. PMID: 30507698.
    Citations:    Fields:    
  7. Kremen J, Chan YM. Genetic evaluation of disorders of sex development: current practice and novel gene discovery. Curr Opin Endocrinol Diabetes Obes. 2019 02; 26(1):54-59. PMID: 30507699.
    Citations:    Fields:    
  8. Guo MH, Plummer L, Chan YM, Hirschhorn JN, Lippincott MF. Burden Testing of Rare Variants Identified through Exome Sequencing via Publicly Available Control Data. Am J Hum Genet. 2018 10 04; 103(4):522-534. PMID: 30269813.
    Citations:    Fields:    
  9. Lippincott MF, Nguyen K, Delaney A, Chan YM, Seminara SB. Assessing Sex Steroid Influence on Kisspeptin Responsiveness in Idiopathic Hypogonadotropic Hypogonadism. J Endocr Soc. 2018 Nov 01; 2(11):1293-1305. PMID: 30430143.
  10. Zhu J, Kusa TO, Chan YM. Genetics of pubertal timing. Curr Opin Pediatr. 2018 08; 30(4):532-540. PMID: 29771761.
    Citations:    Fields:    
  11. Diamond DA, Swartz J, Tishelman A, Johnson J, Chan YM. Management of pediatric patients with DSD and ambiguous genitalia: Balancing the child's moral claims to self-determination with parental values and preferences. J Pediatr Urol. 2018 10; 14(5):416.e1-416.e5. PMID: 29903608.
    Citations:    Fields:    
  12. Chan YM, Lippincott MF, Kusa TO, Seminara SB. Divergent responses to kisspeptin in children with delayed puberty. JCI Insight. 2018 04 19; 3(8). PMID: 29669934.
    Citations:    Fields:    
  13. Shahab M, Lippincott M, Chan YM, Davies A, Merino PM, Plummer L, Mericq V, Seminara S. Discordance in the Dependence on Kisspeptin Signaling in Mini Puberty vs Adolescent Puberty: Human Genetic Evidence. J Clin Endocrinol Metab. 2018 04 01; 103(4):1273-1276. PMID: 29452377.
    Citations:    Fields:    Translation:HumansCells
  14. Chan YM, Balza R, High FA. Case 3-2018: A 5-Month-Old Boy with Hypoglycemia. N Engl J Med. 2018 Jan 25; 378(4):381-389. PMID: 29365308.
    Citations:    Fields:    Translation:Humans
  15. Lippincott MF, Chan YM, Rivera Morales D, Seminara SB. Continuous Kisspeptin Administration in Postmenopausal Women: Impact of Estradiol on Luteinizing Hormone Secretion. J Clin Endocrinol Metab. 2017 06 01; 102(6):2091-2099. PMID: 28368443.
    Citations:    Fields:    Translation:Humans
  16. Zhu J, Chan YM. Adult Consequences of Self-Limited Delayed Puberty. Pediatrics. 2017 Jun; 139(6). PMID: 28562264.
    Citations: 2     Fields:    Translation:Humans
  17. Kremen J, Chan YM, Swartz JM. Recent findings on the genetics of disorders of sex development. Curr Opin Urol. 2017 01; 27(1):1-6. PMID: 27798415.
    Citations:    Fields:    Translation:Humans
  18. Swartz JM, Ciarlo R, Guo MH, Abrha A, Weaver B, Diamond DA, Chan YM, Hirschhorn JN. A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant. Horm Res Paediatr. 2017; 87(3):191-195. PMID: 27855412.
    Citations: 3     Fields:    Translation:HumansCells
  19. Nokoff NJ, Palmer B, Mullins AJ, Aston CE, Austin P, Baskin L, Bernabé K, Chan YM, Cheng EY, Diamond DA, Fried A, Frimberger D, Galan D, Gonzalez L, Greenfield S, Kolon T, Kropp B, Lakshmanan Y, Meyer S, Meyer T, Mullins LL, Paradis A, Poppas D, Reddy P, Schulte M, Reyes KJ, Swartz JM, Wolfe-Christensen C, Yerkes E, Wisniewski AB. Prospective assessment of cosmesis before and after genital surgery. J Pediatr Urol. 2017 Feb; 13(1):28.e1-28.e6. PMID: 27887913.
    Citations: 1     Fields:    
  20. Swartz JM, Ciarlo R, Guo MH, Abrha A, Diamond DA, Chan YM, Hirschhorn JN. Two Unrelated Undervirilized 46,XY Males with Inherited NR5A1 Variants Identified by Whole-Exome Sequencing. Horm Res Paediatr. 2017; 87(4):264-270. PMID: 27553487.
    Citations: 5     Fields:    Translation:HumansCells
  21. Guo MH, Dauber A, Lippincott MF, Chan YM, Salem RM, Hirschhorn JN. Determinants of Power in Gene-Based Burden Testing for Monogenic Disorders. Am J Hum Genet. 2016 09 01; 99(3):527-539. PMID: 27545677.
    Citations: 2     Fields:    Translation:Humans
  22. Richards MR, Plummer L, Chan YM, Lippincott MF, Quinton R, Kumanov P, Seminara SB. Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies. J Med Genet. 2017 01; 54(1):19-25. PMID: 27512013.
    Citations: 3     Fields:    Translation:HumansCells
  23. Lippincott MF, Chan YM, Delaney A, Rivera-Morales D, Butler JP, Seminara SB. Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty. J Clin Endocrinol Metab. 2016 08; 101(8):3061-9. PMID: 27214398.
    Citations: 4     Fields:    Translation:HumansCellsCTClinical Trials
  24. Fullerton BS, Sparks EA, Hall AM, Chan YM, Duggan C, Lund DP, Modi BP, Jaksic T, Hendren WH. Growth morbidity in patients with cloacal exstrophy: a 42-year experience. J Pediatr Surg. 2016 Jun; 51(6):1017-21. PMID: 27114306.
    Citations: 1     Fields:    Translation:Humans
  25. Zhu J, Chan YM. Fertility Issues for Patients with Hypogonadotropic Causes of Delayed Puberty. Endocrinol Metab Clin North Am. 2015 Dec; 44(4):821-34. PMID: 26568495.
    Citations:    Fields:    Translation:Humans
  26. Zhu J, Choa RE, Guo MH, Plummer L, Buck C, Palmert MR, Hirschhorn JN, Seminara SB, Chan YM. A shared genetic basis for self-limited delayed puberty and idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2015 Apr; 100(4):E646-54. PMID: 25636053.
    Citations: 10     Fields:    Translation:Humans
  27. True C, Nasrin Alam S, Cox K, Chan YM, Seminara SB. Neurokinin B is critical for normal timing of sexual maturation but dispensable for adult reproductive function in female mice. Endocrinology. 2015 Apr; 156(4):1386-97. PMID: 25574869.
    Citations: 10     Fields:    Translation:AnimalsCells
  28. Chan YM, Lippincott MF, Butler JP, Sidhoum VF, Li CX, Plummer L, Seminara SB. Exogenous kisspeptin administration as a probe of GnRH neuronal function in patients with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2014 Dec; 99(12):E2762-71. PMID: 25226293.
    Citations: 4     Fields:    Translation:HumansCells
  29. Calder M, Chan YM, Raj R, Pampillo M, Elbert A, Noonan M, Gillio-Meina C, Caligioni C, Bérubé NG, Bhattacharya M, Watson AJ, Seminara SB, Babwah AV. Implantation failure in female Kiss1-/- mice is independent of their hypogonadic state and can be partially rescued by leukemia inhibitory factor. Endocrinology. 2014 Aug; 155(8):3065-78. PMID: 24877624.
    Citations: 9     Fields:    Translation:Animals
  30. Popa SM, Moriyama RM, Caligioni CS, Yang JJ, Cho CM, Concepcion TL, Oakley AE, Lee IH, Sanz E, Amieux PS, Caraty A, Palmiter RD, Navarro VM, Chan YM, Seminara SB, Clifton DK, Steiner RA. Redundancy in Kiss1 expression safeguards reproduction in the mouse. Endocrinology. 2013 Aug; 154(8):2784-94. PMID: 23736293.
    Citations: 12     Fields:    Translation:AnimalsCells
  31. Margolin DH, Kousi M, Chan YM, Lim ET, Schmahmann JD, Hadjivassiliou M, Hall JE, Adam I, Dwyer A, Plummer L, Aldrin SV, O'Rourke J, Kirby A, Lage K, Milunsky A, Milunsky JM, Chan J, Hedley-Whyte ET, Daly MJ, Katsanis N, Seminara SB. Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination. N Engl J Med. 2013 May 23; 368(21):1992-2003. PMID: 23656588.
    Citations: 50     Fields:    Translation:HumansAnimalsCells
  32. Liu Z, Ren C, Jones W, Chen P, Seminara SB, Chan YM, Smith NF, Covey JM, Wang J, Chan KK. LC-MS/MS quantification of a neuropeptide fragment kisspeptin-10 (NSC 741805) and characterization of its decomposition product and pharmacokinetics in rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 May 01; 926:1-8. PMID: 23524040.
    Citations: 4     Fields:    Translation:AnimalsCells
  33. Sidhoum VF, Chan YM, Lippincott MF, Balasubramanian R, Quinton R, Plummer L, Dwyer A, Pitteloud N, Hayes FJ, Hall JE, Martin KA, Boepple PA, Seminara SB. Reversal and relapse of hypogonadotropic hypogonadism: resilience and fragility of the reproductive neuroendocrine system. J Clin Endocrinol Metab. 2014 Mar; 99(3):861-70. PMID: 24423288.
    Citations: 24     Fields:    Translation:Humans
  34. Chan YM. Effects of kisspeptin on hormone secretion in humans. Adv Exp Med Biol. 2013; 784:89-112. PMID: 23550003.
    Citations: 6     Fields:    Translation:HumansCells
  35. Chan YM, Butler JP, Sidhoum VF, Pinnell NE, Seminara SB. Kisspeptin administration to women: a window into endogenous kisspeptin secretion and GnRH responsiveness across the menstrual cycle. J Clin Endocrinol Metab. 2012 Aug; 97(8):E1458-67. PMID: 22577171.
    Citations: 17     Fields:    Translation:Humans
  36. Yang JJ, Caligioni CS, Chan YM, Seminara SB. Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mice and men. Endocrinology. 2012 Mar; 153(3):1498-508. PMID: 22253416.
    Citations: 33     Fields:    Translation:HumansAnimalsCells
  37. Lewkowitz-Shpuntoff HM, Hughes VA, Plummer L, Au MG, Doty RL, Seminara SB, Chan YM, Pitteloud N, Crowley WF, Balasubramanian R. Olfactory phenotypic spectrum in idiopathic hypogonadotropic hypogonadism: pathophysiological and genetic implications. J Clin Endocrinol Metab. 2012 Jan; 97(1):E136-44. PMID: 22072740.
    Citations: 16     Fields:    Translation:Humans
  38. Chan YM, Broder-Fingert S, Paraschos S, Lapatto R, Au M, Hughes V, Bianco SD, Min L, Plummer L, Cerrato F, De Guillebon A, Wu IH, Wahab F, Dwyer A, Kirsch S, Quinton R, Cheetham T, Ozata M, Ten S, Chanoine JP, Pitteloud N, Martin KA, Schiffmann R, Van der Kamp HJ, Nader S, Hall JE, Kaiser UB, Seminara SB. GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1. J Clin Endocrinol Metab. 2011 Nov; 96(11):E1771-81. PMID: 21880801.
    Citations: 19     Fields:    Translation:HumansAnimals
  39. Chan YM. A needle in a haystack: mutations in GNRH1 as a rare cause of isolated GnRH deficiency. Mol Cell Endocrinol. 2011 Oct 22; 346(1-2):51-6. PMID: 21722705.
    Citations: 1     Fields:    Translation:HumansAnimals
  40. Chan YM, Butler JP, Pinnell NE, Pralong FP, Crowley WF, Ren C, Chan KK, Seminara SB. Kisspeptin resets the hypothalamic GnRH clock in men. J Clin Endocrinol Metab. 2011 Jun; 96(6):E908-15. PMID: 21470997.
    Citations: 28     Fields:    Translation:Humans
  41. Wahab F, Ullah F, Chan YM, Seminara SB, Shahab M. Decrease in hypothalamic Kiss1 and Kiss1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res. 2011 Feb; 43(2):81-5. PMID: 21154197.
    Citations: 10     Fields:    Translation:AnimalsCells
  42. Chan YM, Fenoglio-Simeone KA, Paraschos S, Muhammad L, Troester MM, Ng YT, Johnsonbaugh RE, Coons SW, Prenger EC, Kerrigan JF, Seminara SB. Central precocious puberty due to hypothalamic hamartomas correlates with anatomic features but not with expression of GnRH, TGFalpha, or KISS1. Horm Res Paediatr. 2010; 73(5):312-9. PMID: 20389100.
    Citations: 4     Fields:    Translation:Humans
  43. Chan YM, Broder-Fingert S, Wong KM, Seminara SB. Kisspeptin/Gpr54-independent gonadotrophin-releasing hormone activity in Kiss1 and Gpr54 mutant mice. J Neuroendocrinol. 2009 Dec; 21(12):1015-23. PMID: 19840236.
    Citations: 36     Fields:    Translation:Animals
  44. Chan YM, de Guillebon A, Lang-Muritano M, Plummer L, Cerrato F, Tsiaras S, Gaspert A, Lavoie HB, Wu CH, Crowley WF, Amory JK, Pitteloud N, Seminara SB. GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2009 Jul 14; 106(28):11703-8. PMID: 19567835.
    Citations: 51     Fields:    Translation:HumansCells
  45. Chan YM, Broder-Fingert S, Seminara SB. Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men. Peptides. 2009 Jan; 30(1):42-8. PMID: 18644412.
    Citations: 10     Fields:    Translation:HumansAnimals
  46. Chan YC, Burgunder JM, Wilder-Smith E, Chew SE, Lam-Mok-Sing KM, Sharma V, Ong BK. Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation. J Clin Neurosci. 2008 Aug; 15(8):891-4. PMID: 18313928.
    Citations: 8     Fields:    Translation:Humans
  47. Chan YM, Laffel LM. Transition from insulin to glyburide in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11. Pediatr Diabetes. 2007 Aug; 8(4):235-8. PMID: 17659066.
    Citations: 6     Fields:    Translation:Humans
  48. Lapatto R, Pallais JC, Zhang D, Chan YM, Mahan A, Cerrato F, Le WW, Hoffman GE, Seminara SB. Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice. Endocrinology. 2007 Oct; 148(10):4927-36. PMID: 17595229.
    Citations: 153     Fields:    Translation:AnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.