Cell Signaling & Molecular Pharmacology Lab · Yonsei University
Cells are constantly exposed to metabolites, drugs, hormones, and sensory molecules. G protein-coupled receptors (GPCRs) help cells decide what those chemicals mean. We ask three simple questions: What does a receptor sense? Which pathway does it choose? And can we redesign that choice to control cell function?
We answer these questions with GPCRome-scale screening and quantitative signaling assays, then use receptor engineering, structural insight, and computation to turn mechanisms into new ligands and chemogenetic tools.
Screen the GPCRome
From chemical sensing
to selective signaling.
Research questions
A chemical arrives. A receptor senses it. The receptor chooses a pathway. The cell changes its behavior. We study the rules behind each step — and use those rules to discover new ligands and build new ways to control signaling. Across these questions, we are particularly interested in GPCRs that connect chemical sensing to physiology, including receptors that shape itch, pain, and related sensory responses.
Chemical sensing · ligand selectivity · target identification · GPCR screening
We discover which chemicals activate or block GPCRs, and why some receptors recognize one molecule but not another. Target-focused and GPCRome-scale screens give us the first hit; concentration–response testing, orthogonal assays, and receptor counter-screens tell us whether that interaction is real and selective. We are especially interested in understudied, sensory, and orphan GPCRs whose chemical biology is still poorly understood.
G protein selectivity · non-canonical coupling · β-arrestin · signaling bias
Binding a ligand is only the beginning. Once a GPCR turns on, it can choose among several intracellular partners and produce very different outcomes. We map those choices with a 14-Gα BRET panel together with β-arrestin, cAMP, and Ca2+ assays. This lets us uncover non-canonical coupling, signaling bias, partial or inverse agonism, and allosteric effects — and ask why the same receptor behaves differently with different ligands or in different molecular contexts.
Chemogenetics · DREADDs · receptor engineering · precise control of signaling
Once we understand what a receptor senses and which pathway it chooses, we can begin to change those rules. We combine receptor mutagenesis, ligand profiling, structural insight, and iterative screening to build receptor–ligand systems with new selectivity or signaling behavior. Chemogenetic receptors turn this idea into a practical tool: a defined drug can control a defined receptor and, in turn, a defined cellular function.
Selected papers
Selected work across the questions that define the lab today: what GPCRs recognize, which pathways they choose, and how those principles can be used to discover ligands and engineer new receptor systems.
Pharmacological modulation of GPR84 revealed by dual-state structures and immune functional assays
Choi MK†, Park DJ†, Kim P†, Choi HS, Myung S, Yoo Y, Chang N, Yoon GY, Kang HJ#, Ha SJ#, Cho HS# · †co-first · #co-corresponding
Structure-guided design of a peripherally restricted chemogenetic system
Kang HJ*, Krumm BE*, Tassou A*, Geron M*, DiBerto JF, Kapolka NJ, … Fay JF, Scherrer G, Roth BL · *equal contribution
Chemogenetics for cell-type-specific modulation of signalling and neuronal activity
Kang HJ#, Minamimoto T, Wess J, Roth BL# · #corresponding author
Structure, function and pharmacology of human itch GPCRs
Cao C*, Kang HJ*, Singh I, Chen H, Zhang C, Ye W, … Shoichet BK, Fay JF, Roth BL · *equal contribution
Structural insights into the human niacin receptor HCA2–Gi signalling complex
Yang Y*, Kang HJ*, Gao R*, Wang J, Han GW, DiBerto JF, … Roth BL, Rao Z, Liu ZJ · *equal contribution
Virtual discovery of melatonin receptor ligands to modulate circadian rhythms
Stein RM*, Kang HJ*, McCorvy JD*, Glatfelter GC*, … Shoichet BK, Roth BL, Dubocovich ML · *equal contribution
Pryce KD*, Kang HJ*, Sakloth F*, Liu Y, Khan S, Toth K, Kapoor A, … Che T, Qin L, et al. · *equal contribution
Determinants of endogenous ligand specificity divergence among metabotropic glutamate receptors
Kang HJ, Wilkins AD, Lichtarge O, Wensel TG
Kang HJ, Menlove K, Ma J, Wilkins A, Lichtarge O, Wensel TG
Full list
Pharmacological modulation of GPR84 revealed by dual-state structures and immune functional assays
Experimental & Molecular Medicine · Choi MK†, Park DJ†, Kim P†, Choi HS, Myung S, Yoo Y, Chang N, Yoon GY, Kang HJ#, Ha SJ#, Cho HS#
Organelle contact reorganization drives calcium-dependent autophagy under proteostatic stress
Autophagy · Ko Y, Ko M, Ueffing M, Kang HJ, Kwon HJ
Biomolecules · Cho YY†, Kim S†, Kim P, Jo MJ, Park SE, Choi Y, Jung SM*, Kang HJ*
Structure-guided design of a peripherally restricted chemogenetic system
Cell · Kang HJ*, Krumm BE*, Tassou A*, Geron M*, DiBerto JF, Kapolka NJ, Gumpper RH, … Scherrer G, Roth BL
Chemogenetics for cell-type-specific modulation of signalling and neuronal activity
Nature Reviews Methods Primers · Kang HJ#, Minamimoto T, Wess J, Roth BL#
Docking for EP4R antagonists active against inflammatory pain
Nature Communications · Gahbauer S, DeLeon C, Braz JM, Craik V, Kang HJ, Wan X, … Roth BL, Shoichet BK
Structural insights into the human niacin receptor HCA2–Gi signalling complex
Nature Communications · Yang Y*, Kang HJ*, Gao R*, Wang J, Han GW, DiBerto JF, … Rao Z, Liu ZJ
Neurotensin receptor allosterism revealed in complex with a biased allosteric modulator
Biochemistry · Krumm BE, DiBerto JF, Olsen RHJ, Kang HJ, Slocum ST, Zhang S, … Kenakin T, Roth BL
Target deconvolution studies of (2R,6R)-hydroxynorketamine: an elusive search
Molecular Psychiatry · Bonaventura J, Gomez JL, Carlton ML, Lam S, Sanchez-Soto M, … Kang HJ, … Zarate CA Jr, Michaelides M
Journal of Medicinal Chemistry · Yuan G, Dhaynaut M, Guehl NJ, Afshar S, Huynh D, … Kang HJ, … Normandin MD, Brownell AL
Design and discovery of a high affinity, selective and β-arrestin biased 5-HT7 receptor agonist
Medicinal Chemistry Research · Onyameh EK, Ofori E, Bricker BA, Gonela UM, Eyunni SVK, Kang HJ, Voshavar C, Ablordeppey SY
Journal of Medicinal Chemistry · Yuan G, Dhaynaut M, Lan Y, Guehl NJ, Huynh D, … Kang HJ, … Normandin MD, Brownell AL
Structure, function and pharmacology of human itch GPCRs
Nature · Cao C*, Kang HJ*, Singh I, Chen H, Zhang C, Ye W, … Shoichet B, Fay JF, Roth BL
Neuropharmacology · Pryce KD*, Kang HJ*, Sakloth F*, Liu Y, Khan S, Toth K, … Che T, Qin L, et al.
Molecular Imaging and Biology · Yuan G, Guehl NJ, Zheng B, Qu X, Moon SH, Dhaynaut M, … Kang HJ, Zhang Z, et al.
Virtual discovery of melatonin receptor ligands to modulate circadian rhythms
Nature · Stein RM*, Kang HJ*, McCorvy JD*, Glatfelter GC*, Jones AJ, Che T, … Roth BL, Dubocovich ML
Journal of Medicinal Chemistry · Yuan G, Qu X, Zheng B, Neelamegam R, Afshar S, Iyengar S, Pan C, Wang J, Kang HJ, Ondrechen MJ, et al.
Journal of Nuclear Medicine · Wang J, Shoup T, Qu X, Kang HJ, El Fakhri G, Zhang Z, Brownell AL
Nature Communications · McCarroll MN, Gendelev L, Kinser R, Taylor J, Bruni G, … Kang HJ, … Keiser MJ, Kokel D
Evaluation of SYA16263 as a new potential antipsychotic agent without catalepsy
Pharmacology Biochemistry and Behavior · Bricker BA, Peprah K, Kang HJ, Ablordeppey SY
Isoxazolo[3,4-d]pyridazinones positively modulate the metabotropic glutamate subtypes 2 and 4
Bioorganic & Medicinal Chemistry · Gates C, Backos DS, Reigan P, Kang HJ, Koerner C, Mirzaei J, Natale NR
Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin
The FASEB Journal · Le Gonidec S, Chaves-Almagro C, Bai Y, Kang HJ, Smith A, … Caron MG, Valet P, Audigier Y, Masri B
A novel negative allosteric modulator for imaging of metabotropic glutamate receptor 2
ACS Chemical Neuroscience · Zhang X, Kumata K, Yamasaki T, Cheng R, Hatori A, … Kang HJ, … Zhang MR, Liang SH
Journal of Pharmacology and Experimental Therapeutics · Can A, Zanos P, Moaddel R, Kang HJ, Dossou KSS, … Frost DO, Huang XP, Gould TD
Development of CNS multi-receptor ligands: modification of known D2 pharmacophores
Bioorganic & Medicinal Chemistry · Etukala JR, Zhu XY, Eyunni SVK, Onyameh EK, Ofori E, Bricker BA, Kang HJ, Huang XP, Roth BL, Ablordeppey SY
Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands
Bioorganic & Medicinal Chemistry · Ofori E, Zhu XY, Etukala JR, Peprah K, Jordan KR, Adkins AA, Bricker BA, Kang HJ, Huang XP, Roth BL
Bioorganic & Medicinal Chemistry Letters · Zhang Z, Kil KE, Poutiainen P, Choi JK, Kang HJ, Huang XP, Roth BL, Brownell AL
Determinants of endogenous ligand specificity divergence among metabotropic glutamate receptors
Journal of Biological Chemistry · Kang HJ, Wilkins AD, Lichtarge O, Wensel TG
Journal of Biological Chemistry · Kang HJ, Menlove K, Ma J, Wilkins A, Lichtarge O, Wensel TG
* equal contribution · # corresponding author · † equal contribution (first authors). Titles link to the publisher record.
Principal investigator
Hye Jin Kang is an Associate Professor in the Department of Biotechnology at Yonsei University. Her research asks how GPCRs recognize chemical signals, choose intracellular pathways, and can be engineered to control cell function.
Her lab combines receptor-scale screening, quantitative pharmacology, molecular engineering, and structural and computational approaches.
Graduate researchers
.JPG)
JO, Min Jeong
M.S.–Ph.D. Integrated · since 2024.03
Ligand discovery and pharmacology in sensory signaling
PARK, Song E
M.S.–Ph.D. Integrated · since 2024.09
GPCR signaling and receptor pharmacology
WOO, Subin
M.S. · since 2025.03
GPCRome-scale screening and ligand discovery
JO, Eunha
M.S. · since 2025.03
Chemical sensing at the cell–environment interface
LEE, Sujin
Ph.D. · since 2025.03
AI- and structure-guided GPCR drug discovery
MYEONG, Sorin
M.S.–Ph.D. Integrated · since 2026.03
Chemogenetic receptor engineering and signaling bias
CHOI, Yujin
M.S.–Ph.D. Integrated · since 2026.03
Sensory GPCR pharmacology and signaling
KIM, Jisu
M.S. · since 2026.03
Chemosensory receptor pharmacology
JANG, Dongha
M.S.–Ph.D. Integrated · since 2026.03
GPCR pharmacology and mechanism-guided drug discovery
Alumni
KIM, Pankyung
M.S. alumnus
Ahn-Gook Pharmaceutical
CHO, Yun Yeong
M.S. alumna
Contact
Graduate applicants. We are recruiting Ph.D. students and M.S.–Ph.D. integrated students. Please include a CV, academic transcript, and a brief note about your research background and interests.
Undergraduate internships. Please contact the lab 3–4 months before your intended start date.
Where we are
Elsewhere