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Christopher G Bunick, MD/PhD

Associate Professor of Dermatology

Contact Information

Christopher G Bunick, MD/PhD

Mailing Address

  • PO Box 208059

    New Haven, CT 06520-8059

    United States

Dermatology Research in Christopher Bunick Laboratory

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Research Summary

Dr. Bunick uses structural biology techniques called x-ray crystallography, nuclear magnetic resonance, and cryo-electron microscopy to determine the high resolution, three-dimensional structures of proteins important to both normal and diseased skin. Knowing the structure of various skin proteins enables a better understand of how a protein functions in normal and diseased skin states. Ultimately, it may lead to the development of novel therapies.

Specialized Terms: structural biology of skin proteins; x-ray crystallography; epidermal structure and function; structure-based drug design; cryo-EM; NMR

Extensive Research Description

Dr. Christopher Bunick, MD, PhD, is an Associate Professor of Dermatology performing dermatologic research studying the three-dimensional structures of skin-related proteins using primarily x-ray crystallography and cryo-electron microscopy. Dr. Bunick has 25 years of experience in the field of structural biology. He leads a structural biology research program in the dermatology field, with a specific niche: “atomic resolution dermatology.” Dr. Bunick’s research focuses on determining the atomic resolution structures of proteins and protein complexes essential to formation of a functional human skin barrier. He uses x-ray crystallography and cryo-electron microscopy to determine the high resolution, three-dimensional structures of proteins important to both normal and diseased skin. Knowing the structure of various skin proteins enables a better understanding of how a protein functions in normal and diseased skin states. Ultimately, it may lead to the development of novel therapies.


Two recent proteins studied are human profilaggrin and the keratin 1/10 complex because of their importance to skin barrier integrity and association with clinically relevant skin diseases. The NIH/NIAMS website estimates up to 90 million Americans suffer from some form of atopic dermatitis. Atopic dermatitis and other forms of severely dry skin, such as ichthyosis vulgaris, are associated with defects or mutations in profilaggrin and its processed fragment, filaggrin. Similarly, mutations mapped to keratins 1 or 10 are linked to several clinical disorders of keratinization (keratinopathies). Work on these proteins led to a 2.2 Å resolution crystal structure of the profilaggrin S100 calcium-binding domain and several 2.0 Å to 3.3 Å resolution crystal structures of complexes between the 1B and 2B helices of K1 and K10.


In addition to skin barrier research, Dr. Bunick's lab is focused on understanding the biochemical mechanisms of dermatologic drugs. Recent work on the structural mechanism of the acne vulgaris drug sarecycline was published in PNAS, and there are ongoing drug development projects in the lab in acne vulgaris, psoriasis, cancer, and more.

Dr. Bunick currently is funded by the NIH/NIAMS (R01 and R03 Awards) and a research grant from Almirall. His laboratory is open to medical students, graduate students, and post-docs motivated by and passionate for applying biochemistry and structural biology to skin disease.

Coauthors

Research Interests

Biochemistry; Biophysics; Dermatitis, Atopic; Dermatology; Epidermis; Intermediate Filaments; Keratins; Molecular Biology; Skin; Ichthyosis Vulgaris; Crystallography, X-Ray; Computational Biology; Proteomics

Public Health Interests

Cancer

Research Images

X-ray crystal structure of sarecycline bound to bacterial ribosome
Acne vulgaris drug sarecycline binds to the 30S subunit of the bacterial ribosome (gray 16S-rRNA) as well as makes contact with mRNA through its unique C-7 moiety.

Selected Publications

  • Patient and physician perspectives on teledermatology at an academic dermatology department amid the COVID-19 pandemic.Asabor EN, Bunick CG, Cohen JM, Perkins SH. Patient and physician perspectives on teledermatology at an academic dermatology department amid the COVID-19 pandemic. Journal Of The American Academy Of Dermatology 2021, 84: 158-161. PMID: 32946971, PMCID: PMC7491373, DOI: 10.1016/j.jaad.2020.09.029.
  • Recent insight into intermediate filament structure.Eldirany SA, Lomakin IB, Ho M, Bunick CG. Recent insight into intermediate filament structure. Current Opinion In Cell Biology 2021, 68: 132-143. PMID: 33190098, PMCID: PMC7925366, DOI: 10.1016/j.ceb.2020.10.001.
  • Spectrum of Antibiotic Activity and Its Relevance to the Microbiome.Grada A, Bunick CG. Spectrum of Antibiotic Activity and Its Relevance to the Microbiome. JAMA Network Open 2021, 4: e215357. PMID: 33914053, DOI: 10.1001/jamanetworkopen.2021.5357.
  • Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation.Bunick CG, Keri J, Tanaka SK, Furey N, Damiani G, Johnson JL, Grada A. Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation. Antibiotics (Basel, Switzerland) 2021, 10 PMID: 33920812, PMCID: PMC8071131, DOI: 10.3390/antibiotics10040439.
  • Dermatomyositis associated with an adrenal adenoma.Eldirany SA, Ring N, Laskin W, Bunick CG. Dermatomyositis associated with an adrenal adenoma. JAAD Case Reports 2021, 12: 70-73. PMID: 34041336, PMCID: PMC8141419, DOI: 10.1016/j.jdcr.2021.04.012.
  • Genotype‒Structurotype‒Phenotype Correlations in Patients with Pachyonychia Congenita.Wu TT, Eldirany SA, Bunick CG, Teng JMC. Genotype‒Structurotype‒Phenotype Correlations in Patients with Pachyonychia Congenita. The Journal Of Investigative Dermatology 2021, 141: 2876-2884.e4. PMID: 34116063, DOI: 10.1016/j.jid.2021.03.035.
  • Successful management of malodor from fungating tumors using crushed metronidazole tablets.Hu JK, Ligtenberg KG, Leventhal J, Bunick CG. Successful management of malodor from fungating tumors using crushed metronidazole tablets. JAAD Case Reports 2020, 6: 26-29. PMID: 31909133, PMCID: PMC6938872, DOI: 10.1016/j.jdcr.2019.10.025.
  • Ixekizumab-induced alopecia areata.Eldirany SA, Myung P, Bunick CG. Ixekizumab-induced alopecia areata. JAAD Case Reports 2020, 6: 51-53. PMID: 31909139, PMCID: PMC6938813, DOI: 10.1016/j.jdcr.2019.10.012.
  • The Interface between Keratin Structurotype and Human Disease.Eldirany SA, Ho M, Bunick CG. The Interface between Keratin Structurotype and Human Disease. Structure (London, England : 1993) 2020, 28: 271-273. PMID: 32130887, PMCID: PMC7252399, DOI: 10.1016/j.str.2020.02.002.
  • Crystal Structure of Keratin 1/10(C401A) 2B Heterodimer Demonstrates a Proclivity for the C-Terminus of Helix 2B to Form Higher Order Molecular Contacts.Lomakin IB, Hinbest AJ, Ho M, Eldirany SA, Bunick CG. Crystal Structure of Keratin 1/10(C401A) 2B Heterodimer Demonstrates a Proclivity for the C-Terminus of Helix 2B to Form Higher Order Molecular Contacts. The Yale Journal Of Biology And Medicine 2020, 93: 3-17. PMID: 32226330, PMCID: PMC7087056.
  • Structural Basis for How Biologic Medicines Bind their Targets in Psoriasis Therapy.Eldirany SA, Ho M, Bunick CG. Structural Basis for How Biologic Medicines Bind their Targets in Psoriasis Therapy. The Yale Journal Of Biology And Medicine 2020, 93: 19-27. PMID: 32226331, PMCID: PMC7087057.
  • Teledermatology in the era of COVID-19: Experience of an academic department of dermatology.Perkins S, Cohen JM, Nelson CA, Bunick CG. Teledermatology in the era of COVID-19: Experience of an academic department of dermatology. Journal Of The American Academy Of Dermatology 2020, 83: e43-e44. PMID: 32305442, PMCID: PMC7162755, DOI: 10.1016/j.jaad.2020.04.048.
  • CD8+ mycosis fungoides palmaris et plantaris with peripheral blood involvement.Yumeen S, Mirza FN, Lewis JM, Carlson KR, King B, Cowper S, Bunick CG, McNiff J, Girardi M. CD8+ mycosis fungoides palmaris et plantaris with peripheral blood involvement. JAAD Case Reports 2020, 6: 434-437. PMID: 32382639, PMCID: PMC7200192, DOI: 10.1016/j.jdcr.2020.02.025.
  • The new normal: An approach to optimizing and combining in-person and telemedicine visits to maximize patient care.Cohen JM, Bunick CG, Perkins SH. The new normal: An approach to optimizing and combining in-person and telemedicine visits to maximize patient care. Journal Of The American Academy Of Dermatology 2020, 83: e361-e362. PMID: 32593636, PMCID: PMC7316470, DOI: 10.1016/j.jaad.2020.06.075.
  • Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.Batool Z, Lomakin IB, Polikanov YS, Bunick CG. Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20530-20537. PMID: 32817463, PMCID: PMC7456112, DOI: 10.1073/pnas.2008671117.
  • Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteins.Hinbest AJ, Kim SR, Eldirany SA, Lomakin IB, Watson J, Ho M, Bunick CG. Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteins. Journal Of Dermatological Science 2020, 100: 39-49. PMID: 32893105, PMCID: PMC7752840, DOI: 10.1016/j.jdermsci.2020.08.009.
  • Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain.Hinbest AJ, Eldirany SA, Ho M, Bunick CG. Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain. International Journal Of Molecular Sciences 2020, 21 PMID: 32927888, PMCID: PMC7555247, DOI: 10.3390/ijms21186641.
  • More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.Lilly E, Bunick CG, Maley AM, Zhang S, Spraker MK, Theos AJ, Vivar KL, Seminario-Vidal L, Bennett AE, Sidbury R, Ogawa Y, Akiyama M, Binder B, Hadj-Rabia S, Morotti RA, Glusac EJ, Choate KA, Richard G, Milstone LM. More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations. Journal Of The American Academy Of Dermatology 2019, 80: 617-625. PMID: 30287322, PMCID: PMC6372339, DOI: 10.1016/j.jaad.2018.09.042.
  • Human keratin 1/10-1B tetramer structures reveal a knob-pocket mechanism in intermediate filament assembly.Eldirany SA, Ho M, Hinbest AJ, Lomakin IB, Bunick CG. Human keratin 1/10-1B tetramer structures reveal a knob-pocket mechanism in intermediate filament assembly. The EMBO Journal 2019, 38 PMID: 31036554, PMCID: PMC6545558, DOI: 10.15252/embj.2018100741.
  • Alterations in connexin 26 protein structure from lethal keratitis-ichthyosis-deafness syndrome mutations A88V and G45E.Lilly E, Strickler M, Milstone LM, Bunick CG. Alterations in connexin 26 protein structure from lethal keratitis-ichthyosis-deafness syndrome mutations A88V and G45E. Journal Of Dermatological Science 2019, 95: 119-122. PMID: 31331740, PMCID: PMC7263394, DOI: 10.1016/j.jdermsci.2019.07.002.
  • The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease.Bunick CG, Milstone LM. The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease. The Journal Of Investigative Dermatology 2017, 137: 142-150. PMID: 27595935, PMCID: PMC5514376, DOI: 10.1016/j.jid.2016.08.018.
  • Immune-related sarcoidosis observed in combination ipilimumab and nivolumab therapy.Suozzi KC, Stahl M, Ko CJ, Chiang A, Gettinger SN, Siegel MD, Bunick CG. Immune-related sarcoidosis observed in combination ipilimumab and nivolumab therapy. JAAD Case Reports 2016, 2: 264-8. PMID: 27486590, PMCID: PMC4949498, DOI: 10.1016/j.jdcr.2016.05.002.
  • Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27.Bunick CG, Presland RB, Lawrence OT, Pearton DJ, Milstone LM, Steitz TA. Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27. The Journal Of Investigative Dermatology 2015, 135: 1801-1809. PMID: 25760235, PMCID: PMC4466033, DOI: 10.1038/jid.2015.102.
  • Genomic landscape of cutaneous T cell lymphoma.Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, Bjornson RD, Maman Y, Wang T, Tordoff J, Carlson K, Overton JD, Liu KJ, Lewis JM, Devine L, Barbarotta L, Foss FM, Subtil A, Vonderheid EC, Edelson RL, Schatz DG, Boggon TJ, Girardi M, Lifton RP. Genomic landscape of cutaneous T cell lymphoma. Nature Genetics 2015, 47: 1011-9. PMID: 26192916, PMCID: PMC4552614, DOI: 10.1038/ng.3356.
  • Perspectives on physiology and medicine from Nobel Prize Winners: the 64th Lindau Nobel Laureate Meeting.Bunick CG. Perspectives on physiology and medicine from Nobel Prize Winners: the 64th Lindau Nobel Laureate Meeting. The Journal Of Investigative Dermatology 2014, 134: 2853-2855. PMID: 25381760, DOI: 10.1038/jid.2014.358.
  • Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein.Bunick CG, Miller MR, Fuller BE, Fanning E, Chazin WJ. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry 2006, 45: 14965-79. PMID: 17154534, PMCID: PMC2579963, DOI: 10.1021/bi061370o.
  • Keratin 1 as a cell-surface receptor in cancer.Ogunnigbagbe O, Bunick CG, Kaur K. Keratin 1 as a cell-surface receptor in cancer. Biochimica Et Biophysica Acta. Reviews On Cancer 2021, 1877: 188664. PMID: 34890750, DOI: 10.1016/j.bbcan.2021.188664.
  • Sarecycline treatment for acne vulgaris: Rationale for weight-based dosing and limited impact of food intake on clinical efficacy.Grada A, Del Rosso JQ, Graber E, Bunick CG, Stein Gold L, Moore AY, Baldwin H, Obagi Z, Damiani G, Carrothers T, McNamee B, Hanze E. Sarecycline treatment for acne vulgaris: Rationale for weight-based dosing and limited impact of food intake on clinical efficacy. Dermatologic Therapy 2021, e15275. PMID: 34923732, DOI: 10.1111/dth.15275.
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