Siobhan Malany

Siobhan Malany, Ph.D.

Associate Professor

Department: Pharmacodynamics
Business Phone: (352) 273-6004
Business Email: smalany@ufl.edu

About Siobhan Malany

Dr. Siobhan Malany started her pharmacology career in the biotechnology industry in San Diego and moved to Florida in 2011 to lead a chemical biology drug discovery team at the Sanford Burnham Chemical Genomics Center in Orlando. Dr. Malany became interested in space research after networking with administrators at Space Florida and CASIS. Her first launch was on SpaceX CRS-4 after winning a space research competition. She founded Micro-gRx in 2015, with seed funding from Space Florida to develop a human muscle cell system called a “lab-on-chip” that launched to the ISS in 2018. The same year, she transitioned to the College of Pharmacy at the University of Florida where she has advanced an engineered “Human muscle-on-Chip”. These tissue chips launched to the International Space Station in December 2020 to investigate the effects of microgravity on muscle biology. Interviews with Dr. Malany have aired on Channel 6 news and appeared in Authority Magazine Women Leading the Space Industry. She has been a guest on Radio Cade, a podcast from the Cade Museum of Creativity and Invention and on “Houston, we have a podcast,” the official podcast for Johnson Space Center. Dr. Malany holds a Ph.D. in organic chemistry from the University of Iowa and completed postdoctoral training in pharmacology at the University of California, San Diego.

Related Links:

Teaching Profile

Courses Taught
2020-2024
PHA5515 Prin Med Chem-Pcol II
2021-2023
PHA4911 Undergraduate Research in Pharmacodynamics
2021-2024
PHA6910 Supervised Research
2021
PHA6512L Experiential Research Training in Pharmacodynamics
2021-2022
PHA6521C Research Techniques in Pharmacodynamics
2021
PHA6936 Advanced Topics in Pharmaceutical Sciences
2021-2024
PHA7979 Advanced Research
2022-2023
PHA6935 Selected Topics in Pharmacy
2023-2024
PHA7980 Research for Doctoral Dissertation
2023
PHA6185 Life Cycle of a Drug

Research Profile

Research in my laboratory seeks to implement improved in vitro cell based systems to better predict human drug efficacy particularly for age-related diseases by 1) leveraging the physiological relevance of patient-specific cells in combination with phenotypic microscopy and chemogenomic approaches to measure changes in responses to physical stressors; and 2) advance receptor target-based platforms using receptor-specific and selective ligands and mechanistic pharmacology approaches to understand drug mode of action (e.g. kinetics, allosterism).

With funding from NIH-NCATS Tissue Chip Program, we are developing a microphysiological system for age-related muscle wasting (sarcopenia). We are using patient-specific muscle primary cells in 3D culture integrated into a millifluidic device that will be placed on the International Space Station research laboratory to serve as a micro-scale model for studying physical changes induced in microgravity that may mimic aging and for predictive drug and toxicology testing to aide in the development of therapeutics for sarcopenia.

The natriuretic peptide receptors GC-A and GC-B mediate the effects of a family of hormone peptides. Elevated levels of ANP and BNP target the GC-A receptor and provide protection against hypertension and metabolic syndrome; whereas, CNP activation of the GC-B receptor provides anti-fibrotic benefit. We are focused, in collaboration with the Mayo Clinic, on the discoveryofsmallmoleculeallostericpotentiators of GC receptor / cGMP signalingpathway as therapeutics for cardiovascular disease.

The chemokine receptor, CXCR6 is a seven transmembrane domain G protein–coupled receptor (GPCR) target for the natural ligand, CXCL16, a chemokine that attracts natural killer T cells to the liver. We have developed small molecule antagonists targeting the CXCR6/CXCL16 axis to understand mechanism of action and therapeutic potential in liver fibrosis and disease.

Open Researcher and Contributor ID (ORCID)

0000-0003-0710-7460

Publications

2023
Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight
npj Microgravity. 9(1) [DOI] 10.1038/s41526-023-00322-y. [PMID] 37714852.
2023
Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing
Biochemical Pharmacology. 216 [DOI] 10.1016/j.bcp.2023.115764.
2023
Validation of Human Skeletal Muscle Tissue Chip Autonomous Platform to Model Age-Related Muscle Wasting in Microgravity.
Research square. [DOI] 10.21203/rs.3.rs-2631490/v1. [PMID] 37034730.
2022
Biomanufacturing in low Earth orbit for regenerative medicine.
Stem cell reports. 17(1):1-13 [DOI] 10.1016/j.stemcr.2021.12.001. [PMID] 34971562.
2022
Discovery of Small Molecule Activators of Chemokine Receptor CXCR4 That Improve Diabetic Wound Healing
International Journal of Molecular Sciences. 23(4) [DOI] 10.3390/ijms23042196. [PMID] 35216311.
2022
Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells
Aging Cell. 21(7) [DOI] 10.1111/acel.13650. [PMID] 35653714.
2021
Discovery of small molecule guanylyl cyclase A receptor positive allosteric modulators
Proceedings of the National Academy of Sciences. 118(52) [DOI] 10.1073/pnas.2109386118. [PMID] 34930837.
2020
Discovery of small molecule antagonists of chemokine receptor CXCR6 that arrest tumor growth in SK-HEP-1 mouse xenografts as a model of hepatocellular carcinoma.
Bioorganic & medicinal chemistry letters. 30(4) [DOI] 10.1016/j.bmcl.2019.126899. [PMID] 31882297.
2020
Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation
International Journal of Molecular Sciences. 21(24) [DOI] 10.3390/ijms21249557. [PMID] 33334026.
2018
A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis
. 11:1-15
2018
A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis
Disease Models & Mechanisms. 11(9) [DOI] 10.1242/dmm.033530. [PMID] 30254132.
2018
Discovery of Novel Small-Molecule Inducers of Heme Oxygenase-1 That Protect Human iPSC-Derived Cardiomyocytes from Oxidative Stress.
The Journal of pharmacology and experimental therapeutics. 364(1):87-96 [DOI] 10.1124/jpet.117.243717. [PMID] 29101218.
2016
Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility
. 305:250-258
2016
Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility.
Toxicology and applied pharmacology. 305:250-258 [DOI] 10.1016/j.taap.2016.06.025. [PMID] 27343406.
2016
MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling.
The Journal of clinical investigation. 126(9):3567-79 [DOI] 10.1172/JCI87382. [PMID] 27500491.
2015
Design of high-throughput screening assays and identification of a SUMO1-specific small molecule chemotype targeting the SUMO-interacting motif-binding surface.
ACS combinatorial science. 17(4):239-46 [DOI] 10.1021/co500181b. [PMID] 25719760.
2015
Discovery of ML358, a Selective Small Molecule Inhibitor of the SKN-1 Pathway Involved in Drug Detoxification and Resistance in Nematodes.
ACS chemical biology. 10(8):1871-9 [DOI] 10.1021/acschembio.5b00304. [PMID] 25946346.
2015
Targeting α-synuclein oligomers by protein-fragment complementation for drug discovery in synucleinopathies.
Expert opinion on therapeutic targets. 19(5):589-603 [DOI] 10.1517/14728222.2015.1009448. [PMID] 25785645.
2014
Identification of Inhibitors of triacylglyceride accumulation in muscle cells: comparing HTS results from 1536-well plate-based and high-content platforms.
Journal of biomolecular screening. 19(1):77-87 [DOI] 10.1177/1087057113501198. [PMID] 23989452.
2013
An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans.
PloS one. 8(4) [DOI] 10.1371/journal.pone.0062166. [PMID] 23637990.
2012
Lead optimization of 2-(piperidin-3-yl)-1H-benzimidazoles: identification of 2-morpholin- and 2-thiomorpholin-2-yl-1H-benzimidazoles as selective and CNS penetrating H₁-antihistamines for insomnia.
Bioorganic & medicinal chemistry letters. 22(1):421-6 [DOI] 10.1016/j.bmcl.2011.10.115. [PMID] 22153347.
2011
Influence of pKa on the biotransformation of indene H1-antihistamines by CYP2D6.
Bioorganic & medicinal chemistry letters. 21(3):947-51 [DOI] 10.1016/j.bmcl.2010.12.053. [PMID] 21232954.
2010
Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia.
Bioorganic & medicinal chemistry letters. 20(19):5874-8 [DOI] 10.1016/j.bmcl.2010.07.117. [PMID] 20800486.
2010
Novel benzothiophene H1-antihistamines for the treatment of insomnia.
Bioorganic & medicinal chemistry letters. 20(7):2316-20 [DOI] 10.1016/j.bmcl.2010.01.134. [PMID] 20188547.
2010
Selectivity profiling of novel indene H(1)-antihistamines for the treatment of insomnia.
Bioorganic & medicinal chemistry letters. 20(8):2629-33 [DOI] 10.1016/j.bmcl.2010.02.055. [PMID] 20227880.
2010
The discovery and structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective, CNS penetrating H1-antihistamines for insomnia.
Bioorganic & medicinal chemistry letters. 20(9):2916-9 [DOI] 10.1016/j.bmcl.2010.03.027. [PMID] 20347297.
2009
Analytical method for simultaneously measuring ex vivo drug receptor occupancy and dissociation rate: application to (R)-dimethindene occupancy of central histamine H1 receptors.
Journal of receptor and signal transduction research. 29(2):84-93 [DOI] 10.1080/10799890902721339. [PMID] 19308787.
2009
Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.
Bioorganic & medicinal chemistry letters. 19(15):4380-4 [DOI] 10.1016/j.bmcl.2009.05.086. [PMID] 19553115.
2009
Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia.
Journal of medicinal chemistry. 52(17):5307-10 [DOI] 10.1021/jm900933k. [PMID] 19663387.
2009
N-[6-amino-2-(heteroaryl)pyrimidin-4-yl]acetamides as A2A receptor antagonists with improved drug like properties and in vivo efficacy.
Journal of medicinal chemistry. 52(3):709-17 [DOI] 10.1021/jm800908d. [PMID] 19140664.
2008
2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A(2A) antagonists with improved solubility and metabolic stability.
Bioorganic & medicinal chemistry letters. 18(20):5402-5 [DOI] 10.1016/j.bmcl.2008.09.048. [PMID] 18835161.
2008
2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A(2A) antagonists with reduced hERG liability.
Bioorganic & medicinal chemistry letters. 18(4):1269-73 [DOI] 10.1016/j.bmcl.2008.01.036. [PMID] 18249540.
2008
2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituents.
Journal of medicinal chemistry. 51(6):1719-29 [DOI] 10.1021/jm701185v. [PMID] 18307292.
2008
2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 2. Reduction of hERG activity, observed species selectivity, and structure-activity relationships.
Journal of medicinal chemistry. 51(6):1730-9 [DOI] 10.1021/jm701187w. [PMID] 18307293.
2008
Identification of novel, water-soluble, 2-amino-N-pyrimidin-4-yl acetamides as A2A receptor antagonists with in vivo efficacy.
Journal of medicinal chemistry. 51(3):400-6 [DOI] 10.1021/jm070623o. [PMID] 18189346.
2008
Lead optimization of 4-acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A adenosine receptor antagonists for the treatment of Parkinson’s disease.
Journal of medicinal chemistry. 51(22):7099-110 [DOI] 10.1021/jm800851u. [PMID] 18947224.
2008
Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.
Bioorganic & medicinal chemistry letters. 18(6):1778-83 [DOI] 10.1016/j.bmcl.2008.02.032. [PMID] 18329269.
2006
A novel cell-based assay for G-protein-coupled receptor-mediated cyclic adenosine monophosphate response element binding protein phosphorylation.
Journal of biomolecular screening. 11(4):351-8 [PMID] 16751331.
2006
Histamine induces interleukin-6 expression in the human synovial sarcoma cell line (SW982) through the H1 receptor.
Inflammation research : official journal of the European Histamine Research Society … [et al.]. 55(9):393-8 [PMID] 17122961.
2006
Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin-releasing factor1 (CRF1) receptor.
Biochemical pharmacology. 72(2):244-55 [PMID] 16750175.
2001
Point mutations identify the glutamate binding pocket of the N-methyl-D-aspartate receptor as major site of conantokin-G inhibition.
Neuropharmacology. 41(6):753-61 [PMID] 11640930.
2000
Orientation of alpha-neurotoxin at the subunit interfaces of the nicotinic acetylcholine receptor.
Biochemistry. 39(50):15388-98 [PMID] 11112524.
2000
Pairwise electrostatic interactions between alpha-neurotoxins and gamma, delta, and epsilon subunits of the nicotinic acetylcholine receptor.
The Journal of biological chemistry. 275(8):5478-84 [PMID] 10681526.
2000
Subunit interface selective toxins as probes of nicotinic acetylcholine receptor structure.
Pflugers Archiv : European journal of physiology. 440(Suppl 1):R115-R117 [DOI] 10.1007/s004240000028. [PMID] 28008504.
1999
Subunit interface selectivity of the alpha-neurotoxins for the nicotinic acetylcholine receptor.
The Journal of biological chemistry. 274(14):9581-6 [PMID] 10092644.
1999
Theoretical and experimental investigations of electrostatic effects on acetylcholinesterase catalysis and inhibition.
Chemico-biological interactions. 119-120:99-110 [PMID] 10421443.
1998
Toxins selective for subunit interfaces as probes of nicotinic acetylcholine receptor structure.
Journal of physiology, Paris. 92(2):79-83 [PMID] 9782448.

Grants

Mar 2023 ACTIVE
Advancing small molecule CXCR4 agonists for diabetic wound healing
Role: Principal Investigator
Funding: UNIVERSITY OF ARIZONA via NATL INST OF HLTH NIDDK
May 2022 ACTIVE
Preclinical development of CXCR6 antagonists to target sorafenib resistance in Hepatocellular Carcinoma
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
May 2022 ACTIVE
Novel Therapeutics for Cardiovascular Disease
Role: Principal Investigator
Funding: MAYO CLINIC via NATL INST OF HLTH NHLBI
Oct 2021 – Sep 2022
Optimize Guanyl Cyclase Receptor A Potentiators to IND-enabling Studies as Potential Cardiovascular Therapeutics
Role: Principal Investigator
Funding: ALLOROCK
Sep 2020 – Aug 2023
Electrical Stimulation of Human Myocytes in Microgravity: An In Vitro Model to Evaluate Therapeutics to Counteract Muscle Wasting
Role: Principal Investigator
Funding: NATL INST OF HLTH NCATS
Aug 2020 – Aug 2022
Advancing small molecule CXCR4 agonists for diabetic wound healing
Role: Principal Investigator
Funding: UNIV OF COLORADO via NATL INST OF HLTH NIDDK
Jan 2019 – Mar 2022
Transcriptional Gene analysis of human muscle cells grown in microgravity and preserved in a microfluidic lab-on-a-chip.
Role: Principal Investigator
Funding: MICRO-GRX via SPACE FLORIDA
Dec 2018 – Aug 2020
Electrical Stimulation of Human Myocytes in Microgravity: An In Vitro Model to Evaluate Therapeutics to Counteract Muscle Wasting
Role: Principal Investigator
Funding: NATL INST OF HLTH NCATS
Dec 2018 – May 2021
Small Molecule Discovery for Particulate Guanylyl Cyclase Receptor B Enhancers
Role: Principal Investigator
Funding: MAYO CLINIC via NATL INST OF HLTH NIA
Dec 2018 – Nov 2019
Identifying CxCR4 Receptor Agonists to Improve Diabetic Healing
Role: Principal Investigator
Funding: UNIV OF COLORADO DENVER & ANSCHUTZ MED via NATL INST OF HLTH NIDDK

Education

Ph.D.
1997 · University of Iowa
B.A.
1992 · Augustana College

Contact Details

Phones:
Business:
(352) 273-6004
Emails:
Business:
smalany@ufl.edu
Addresses:
Business Mailing:
PO Box 100487
GAINESVILLE FL 32610
Business Street:
MSB P1-31
MSB P1-31
GAINESVILLE FL 326110001