Swati S. More, PhD

Research Summary

Research in my laboratories seeks to identify, describe and solve biological problems through chemical means. Improved understanding of the molecular bases of various pathological and toxicological phenomena are regarded as milestones, with the design and successful development of novel chemical or biological therapeutics and diagnostic tools being the end-goals. A broad range of techniques are employed toward these ends, ranging from animal behavior studies, molecular biology, organic synthesis, rational drug design, biophysics, imaging and microscopy. A keen emphasis is placed on inculcating interdisciplinary research skills in laboratory personnel that would enable them to function as independent researchers.

Research Projects

Currently targeted areas are:

1. Oxidative stress – pathological and toxicological studies, chemoprevention, drug design. Amyloidogenic peptides are established etiological agents of Alzheimer’s and Parkinson’s diseases. We have shown through biophysical and biochemical investigations that the food additive, 2,3-butanedione (diacetyl) is capable of inducing amyloid peptide misfolding in intact cells. Ongoing research seeks to define the relevance of this phenomenon in the intact animal.
The human body utilizes glutathione as a primary cellular reductant. This thiol has been shown to be depleted in conditions of oxidative damage. Administration of glutathione does not lead to the latter’s intact passage to the site of action due to metabolic breakdown by ?-glutamyl transpeptidase. About five decades ago, Prof. Vince envisioned the creation of ?-glutathione (?-GSH) as a means to bypass ?-glutamyl transpeptidase. We have now shown that ?-GSH fulfills cardinal functions of glutathione, establishing it as a candidate for the treatment of a variety of conditions that involve deficiency of glutathione and/or oxidative damage.

2. Drug transport – membrane transporters and their targeting.
The selective localization of membrane bound transport proteins renders attractive the latter’s exploitation for targeted drug delivery. Consequently, we are examining the distribution of membrane transporters in the body through various diagnostic probes and are designing small molecules that would be selectively uptaken by the transporter in question.

3. Imaging and diagnostic tool development.
We are seeking to validate imaging techniques for the identification and measurement of amyloidogenesis.

Vartak, A. P. & More, S. S. (2023). Current Perspective on Amyloid Aggregation Accelerating Properties of the Artificial Butter Flavorant, Diacetyl. Neural Regeneration Research, Just Accepted.

Xie, W., Jiang, R., Vince, R., & More, S. S. (2023) Geometric isomer of guanabenz confers hepatoprotection to a murine model of acetaminophen toxicity. Chemical Research in Toxicology, 36(7), 1071-1080. doi: 10.1021/acs.chemrestox.3c00047.

Yee, S. W., Macdonald, C., Mitrovic, D., Zhou, X., Koleske, M. L., Yang, J., Silva, D. B., Grimes, P. R., Trinidad, D., More, S. S., Kachuri, L., Witte, J. S., Delemotte, L., Giacomini, K. M., Coyote-Maestas, W. (2023) The full spectrum of OCT1 (SLC22A1) mutations bridges transporter biophysics to drug pharmacogenomics. bioRxiv. 2023 Jun 7:2023.06.06.543963. doi: 10.1101/2023.06.06.543963. 

Rao, S. P., Dobariya, P., Bellamkonda, H., & More, S. S. (2023). Role of 3-mercaptopyruvate sulfurtransferase (3-MST) in physiology and disease. Antioxidants, 12(3), 603.  Submitted, 2023. doi: 10.3390/antiox12030603

Xie, W., Cao, B., Zhu, H., Raza, A., Juckel, N., Xie, J., Jiang, R., Vince, R., Lee, Michael K., & More, S. S. (2022). Orally Bioavailable Prodrugs of ψ-GSH: A Potential Treatment for Alzheimer's Disease. Journal of Medicinal Chemistry, 65(21), 14441-144455. doi: 10.1021/acs.jmedchem.2c00779

Rao, S. P., Xie, W., Kwon, C. Y. I., Juckel, N., Xie, J., Dronamraju, V. R., Vince, R., Lee, M. K., & More, S. S. (2022) Sulfanegen Stimulates 3-Mercaptopyruvate Sulfurtransferase Activity and Ameliorates Alzheimer’s Disease Pathology and Oxidative Stress in vivo.. Redox Biology, 57, 102484. doi: 10.1016/j.redox.2022.102484

Raza, A., Xie, W., Kim, K. H., Dronamraju, V. R., Williams, J., Vince, R., & More, S. S. (2022). Dipeptide of ψ-GSH Inhibits Oxidative Stress and Neuroinflammation in an Alzheimer’s Disease Mouse Model. Antioxidants (Basel), 11(6), 1075. doi: 10.3390/antiox11061075

Trieu, B. H., Remmers, B. C., Toddes, C., Brandner, D. D., Lefevre, E. M., Kocharian, A., Retzlaff, C. L., Dick, R. M., Mashal, M. A., Gauthier, E. A., Xie, W., Zhang, Y., More, S.S., & Rothwell, P. E.* (2022). Angiotensin-converting enzyme gates brain circuit-specific plasticity via an endogenous opioid. Science, 375(6585), 1177-1182. doi: 10.1126/science.abl5130

Beach, J. M., Rizvi, M., Lichtenfels, C. B., Vince, R., & More, S. S. (2021). Topical Review: Studies of Ocular Function and Disease Using Hyperspectral Imaging. Optometry and Vision Science, 99(2), 101-113.  doi: 10.1097/OPX.0000000000001853

Xie, J., Jiang, R., Xie, W., Cao, B., & More, S. S. (2021). LC-MS/MS determination of guanabenz E/Z isomers and its application to in vitro and in vivo DMPK profiling studies. Journal of Pharmaceutical and Biomedical Analysis, 205, 114331. doi: https://doi.org/10.1016/j.jpba.2021.114331

Kwon, Y. I. C., Xie, W., Zhu, H., Xie, J., Shinn, K., Juckel, N., Vince, R., More, S. S.*, & Lee, M. K.* (Co-Corresponding Authors) (2021). γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer's Disease-like Pathology and Neurodegeneration in a Mouse Model. Antioxidants, 10(11), 1796. PubMed Central ID Number: PMC8614797 doi: 10.3390/antiox10111796

Xie, W., Kim, K. H., Vince, R., & More, S. S. (2021). The Amyloid Aggregation Accelerator Diacetyl Prevents Cognitive Decline in Alzheimer's Mouse Models. Chemical research in toxicology, 34(5), 1355-1366.  doi: 10.1021/acs.chemrestox.1c00089

Zhu, H., Dronamraju, V., Xie, W., & More, S. S. (2021). Sulfur-containing therapeutics in the treatment of Alzheimer's disease. Medicinal chemistry research: an international journal for rapid communications on design and mechanisms of action of biologically active agents, 30(2), 305-352. PubMed Central ID Number: PMC7889054 doi: 10.1007/s00044-020-02687-1

Xie, W., Xie, J., Vince, R., & More, S. S. (2020). Guanabenz Attenuates Acetaminophen-Induced Liver Toxicity and Synergizes Analgesia in Mice. Chemical research in toxicology, 33(1), 162-171.  doi: 10.1021/acs.chemrestox.9b00162

More, S. S., Beach, J. M., McClelland, C., Mokhtarzadeh, A., & Vince, R. (2019). In Vivo Assessment of Retinal Biomarkers by Hyperspectral Imaging: Early Detection of Alzheimer's Disease. ACS chemical neuroscience, 10(11), 4492-4501.  doi: 10.1021/acschemneuro.9b00331

Singh, R., Xie, W., Williams, J., Vince, R.*, & More, S. S. (2019). Discovery of Anticancer Clinical Candidate, Tosedostat, As an Analgesic Agent. ACS chemical neuroscience, 10(9), 4007-4017.  doi: 10.1021/acschemneuro.9b00230

More, S. S., Nugent, J., Vartak, A. P., Nye, S. M., & Vince, R. (2017). Hepatoprotective Effect of ψ-Glutathione in a Murine Model of Acetaminophen-Induced Liver Toxicity. Chemical research in toxicology, 30(3), 777-784.  doi: 10.1021/acs.chemrestox.6b00291

Wezena, C. A., Urscher, M., Vince, R., More, S. S., & Deponte, M. (2016). Hemolytic and antimalarial effects of tight-binding glyoxalase 1 inhibitors on the host-parasite unit of erythrocytes infected with Plasmodium falciparum. Redox biology, 8, 348-53. PubMed Central ID Number: PMC4789335 doi: 10.1016/j.redox.2016.02.006

More, S. S., Beach, J. M., & Vince, R. (2016). Early Detection of Amyloidopathy in Alzheimer's Mice by Hyperspectral Endoscopy. Investigative ophthalmology & visual science, 57(7), 3231-8.  doi: 10.1167/iovs.15-17406

Ai, T., Wilson, D. J., More, S. S., Xie, J., & Chen, L. (2016). 5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors. Journal of medicinal chemistry, 59(7), 2928-41.  doi: 10.1021/acs.jmedchem.5b01376

More, S. S., & Vince, R. (2015). Hyperspectral imaging signatures detect amyloidopathy in Alzheimer's mouse retina well before onset of cognitive decline. ACS chemical neuroscience, 6(2), 306-15.  doi: 10.1021/cn500242z

Cui, H., Kamal, Z., Ai, T., Xu, Y., More, S. S., Wilson, D. J., & Chen, L. (2014). Discovery of potent and selective sirtuin 2 (SIRT2) inhibitors using a fragment-based approach. Journal of medicinal chemistry, 57(20), 8340-57.  doi: 10.1021/jm500777s

More, S. S., Vartak, A. P., & Vince, R. (2013). Restoration of glyoxalase enzyme activity precludes cognitive dysfunction in a mouse model of Alzheimer's disease. ACS chemical neuroscience, 4(2), 330-8. PubMed Central ID Number: PMC3582295 doi: 10.1021/cn3001679

Vartak, A. P., More, S. S., & Vince, R. (2012). Could the artificial butter flavoring, diacetyl, cause Alzheimer's disease. Neurodegenerative Disease Management, 2, 1-3.  

More, S. S., & Vince, R. (2012). Potential of a γ-glutamyl-transpeptidase-stable glutathione analogue against amyloid-b toxicity. ACS Chemical Neuroscience, 3, 204-210.  

More, S. S., Vartak, A. P., & Vince, R. (2012). The butter flavorant, diacetyl, exacerbates β-amyloid cytotoxicity. Chemical research in toxicology, 25(10), 2083-91.  doi: 10.1021/tx3001016

Urscher, M., More, S. S., Alisch, R., Vince, R., & Deponte, M. (2012). Tight-binding inhibitors efficiently inactivate both reaction centers of monomeric Plasmodium falciparum glyoxalase 1. The FEBS journal, 279(14), 2568-78.  doi: 10.1111/j.1742-4658.2012.08640.x

More, S. S., Raza, A., & Vince, R. (2012). The butter flavorant, diacetyl, forms a covalent adduct with 2-deoxyguanosine, uncoils DNA, and leads to cell death. Journal of agricultural and food chemistry, 60(12), 3311-7.  doi: 10.1021/jf300180e

More, S. S., Itsara, M., Yang, X., Geier, E. G., Tadano, M. K., Seo, Y., Vanbrocklin, H. F., Weiss, W. A., Mueller, S., Haas-Kogan, D. A., Dubbois, S. G., Matthay, K. K., Giacomini, K. M. (2011). Vorinostat increases expression of functional norepinephrine transporter in neuroblastoma in vitro and in vivo model systems. Clinical cancer research : an official journal of the American Association for Cancer Research, 17(8), 2339-49. PubMed Central ID Number: PMC3247296 doi: 10.1158/1078-0432.CCR-10-2949

Li, S., Chen, Y., Zhang, S., More, S. S., Huang, X., & Giacomini, K. M. (2011). Role of organic cation transporter 1, OCT1 in the pharmacokinetics and toxicity of cis-diammine(pyridine)chloroplatinum(II) and oxaliplatin in mice. Pharmaceutical research, 28(3), 610-25. PubMed Central ID Number: PMC3040319 doi: 10.1007/s11095-010-0312-6

Chen, L., Pawlikowski, B., Schlessinger, A., More, S. S., Stryke, D., Johns, S. J., . . . Giacomini, K. M. (2010). Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenetics and genomics, 20(11), 687-99. PubMed Central ID Number: PMC2976715 doi: 10.1097/FPC.0b013e32833fe789

More, S. S., Akil, O., Ianculescu, A. G., Geier, E. G., Lustig, L. R., & Giacomini, K. M. (2010). Role of the copper transporter, CTR1, in platinum-induced ototoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(28), 9500-9. PubMed Central ID Number: PMC2949060 doi: 10.1523/JNEUROSCI.1544-10.2010

More, S. S., Li, S., Yee, S. W., Chen, L., Xu, Z., Jablons, D. M., & Giacomini, K. M. (2010). Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Molecular cancer therapeutics, 9(4), 1058-69. PubMed Central ID Number: PMC3258025 doi: 10.1158/1535-7163.MCT-09-1084

More, S. S., & Vince, R. (2009). Inhibition of glyoxalase I: the first low-nanomolar tight-binding inhibitors. Journal of medicinal chemistry, 52(15), 4650-6.  doi: 10.1021/jm900382u

More, S. S., & Vince, R. (2008). Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs. Journal of medicinal chemistry, 51(15), 4581-8.  doi: 10.1021/jm800239v

Cropp, C. D., Komori, T., Shima, J. E., Urban, T. J., Yee, S. W., More, S. S., & Giacomini, K. M. (2008). Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Molecular pharmacology, 73(4), 1151-8. PubMed Central ID Number: PMC2698938 doi: 10.1124/mol.107.043117

More, S. S., & Vince, R. (2007). Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I. Bioorganic & medicinal chemistry letters, 17(13), 3793-7.  doi: 10.1016/j.bmcl.2006.12.056

More, S. S., & Vince, R. (2006). A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I. Bioorganic & medicinal chemistry letters, 16(23), 6039-42.  doi: 10.1016/j.bmcl.2006.08.121

Research Funding Grants

Retinal Hyperspectral Imaging: A Tool for Early Detection of Alzheimer’s Disease
Duration: 01/01/2019-12/31/2022
Funding Agency: Minnesota Partnership for Biotechnology and Medical Genomics
Role: Principal Investigator (Mayo PI: John J. Chen, Department of ophthalmology, Rochester)

Role of glyoxalase-1 in Alzheimer's disease pathogenesis and therapy                                                                                             Duration: 08/19 - 04/24
Funding Source: NIH/NIA
Role: Principal Investigator (Co-I: Michael Lee, Department of Neuroscience)

Retinal Changes in Alzheimer’s disease (AD) Correlated with Cerebral Amyloid Staging, A Promising Early Biomarker in AD
Duration: 03/21 - 03/24
Funding Source: Alzheimer’s Drug Discovery Foundation (ADDF) – Diagnostics Accelerator Program
Role: Principal Investigator (Site 2 with RetiSpec, Inc.)

Control of Endogenous Opioid Signaling by Domain-Selective Inhibition of Angiotensin Converting Enzyme
Duration: 03/22 - 02/24
Funding Source: OACA Faculty Research Development Grant Program 2021
Role: Co-PI (PI: Patrick Rothwell, Department of Neuroscience)

Domain-specific inhibition of angiotensin converting enzyme as a therapeutic strategy for opioid use disorders
Duration: 07/22 - 06/25
Funding Source: NIH/NIDA
Role: MPI (PI: Patrick Rothwell, Department of Neuroscience)

Monoaminergic neurotransmitter impairment from TBI as an early mechanism in neurodegenerative disease
Duration: 06/23 - 03/27
Funding Source: Henry Jackson Foundation/DOD (USU) 
Role: Co-I (PI: Michael Lee, Department of Neuroscience)

Identification of small molecules that regulate endogenous opioid signaling by inhibiting angiotensin converting enzyme
Duration: 09/22 - 07/27
Funding Source: NIH/NIDA
Role: Principal Investigator (MPI: Patrick Rothwell, Department of Neuroscience)

Vince, R., More, S. S. Methods for the Treatment of Conditions Related to Hydrogen Sulfide. (2022) Case No.: 2020-331; U.S. Pat. Appl. Publ., US 20220023267 A1 20220127 09531.532PV1. 

Vince, R., More, S. S. Methods for the Treatment of Conditions Related to Hydrogen Sulfide. (2021) Case No.: 2020-331; 09531.532PV1. Issued: 2021

Vince, R., More, S. S. Methods for diagnosis of transmissible spongiform encephalopathy in infected animals. (2020), 09531.510PV1 2020-237. Issued: 2020

Vince, R., More, S. S.; Beach, J. M. Spectral-spatial Device. (2020) US 10, 837,830B2; World Intellectual Property Organization, WO2020010021 A1. Issued: 2020

Vince, R., More, S. S.; Raza, A. Therapeutic compounds for treatment of nervous system diseases. PCT Int. Appl. (2020), WO 2020010021 A1 20200109. Issued: 2020

More, S. S., Vince, R. Preparation of therapeutic compounds useful for reducing endoplasmic reticulum stress and for producing analgesia. (2019) Ref. 20160321 09531.426PV1; U.S. Pat. Appl. Publ., US20180230105 A1. Issued: 2019

Vince, R., Singh, R., More, S. S. Use of Tosedostat and related compounds as analgesics. U.S. Pat. Appl. Publ. (2019), US 20190282531 A1 20190919. Issued: 2019

Hyperspectral Imaging Technology for early detection of neurodegenerative disorders was licensed to RetiSpec Inc., Toronto, Canada, 2018. Issued: 2018

More, S. S., Vince, R. (2018) Preparation of therapeutic compounds. U.S. Pat. Appl. Publ. 2018; US 20180230105 A1 20180816. Issued: 2018

Giacomini, K. M., More, S. S., Yee, S. W., Geier, E., Wilson, J. (2017) Platinum anticancer agents. PCT Int. Appl. 2017, WO 2017091616 A1 20170601. Issued: 2017

Vince, R., More, S. S., Beach, J. M. (2017) Spectral-spatial imaging device. PCT Int. Appl. 2017, WO 2017156400 A1 20170914. Issued: 2017

Chen, L., Ai, T., More, S. S. (2016) Preparation of heterocyclic carboxamide derivatives useful as SIRT2 inhibitors. U.S. Pat. Appl. Publ. 2016, US 20160376238 A1 20161229. Issued: 2016

Vince, R., More, S. S. (2014) Glutathione analogs and uses thereof. U.S. Pat. Appl. Publ. 2014, US 20140154192 A1 20140605. Issued: 2014

Vince, R., More, S. S. (2013) Glutathione analogs for treating neurodegenerative disorders. PCT Int. Appl. WO 2013009647 A1 20130117. Issued: 2013

Vince, R., More, S. S. (2013) Hyperspectral imaging for early detection of Alzheimer’s disease. PCT Int. Appl. WO 2013086516 A1 20130613. Issued: 2013

Giacomini, K. M., More, S. S. (2013) Preparation of platinum(II) chloro amine complexes with piperazine as anticancer agents. PCT Int. Appl. WO 2013033041 A1 20130307. Issued: 2013