Susan C Frost

Susan C Frost,

Professor Emeritus

Department: MD-BIOCHEM / MOLECULAR BIOL
Business Phone: (352) 226-2512
Business Email: sfrost@ufl.edu

About Susan C Frost

Dr. Susan C. Frost earned her Ph.D. degree in biochemistry from the University of Arizona in 1979. She was an Adjunct Assistant Professor at Arizona for three years before taking a postdoctoral position in the laboratory of M. Daniel Lane at Johns Hopkins University. Here she studied insulin-dependent glucose transport in adipocytes, funded by NIH. Dr. Frost joined the Faculty at the University of Florida in 1985 and is currently a Professor of Biochemistry and Molecular Biology She has served on multiple editorial boards, and recently finished four years of service on the Diabestes and Kidney Diseases B Subcommittee of NIDDK (2009-2013). She chaired the department from 1996 to 1998 and served as the Director of the BMB Ph.D. program from 2007-2010.

Teaching Profile

Courses Taught
2020-2021
GMS5905 Special Topics in Biomedical Sciences
2008-2009,2011-2018,2014-2019,2018-2019
BCH6209 Advanced Metabolism: Regulation of Key Reactions in Amino Acid and Nucleotide Metabolism
2007-2008,2011-2019,2018-2019
BCH6208 Advanced Metabolism: Regulation of Key Reactions in Carbohydrate and Lipid Metabolism
2007-2009,2011-2016,2013-2018,2015-2019
BCH6207 Advanced Metabolism: Role of Membranes in Signal Transduction and Metabolic Control
2007-2019
BCH6206 Advanced Metabolism
2011-2012,2014-2018
DEN5121 Biochm Molec Cell Bio
2014,2017-2018
BCH4905 Biochemistry Senior Research
2018
GMS7980 Research for Doctoral Dissertation
2007-2011
BCH6876 Recent Advances in Membrane Biology

Research Profile

My laboratory studies the regulation of the microenvironment by carbonic anhydrase (CA) in breast cancer cells. We have known for decades that hypoxic conditions in cancer cells lead to the upregulation of the GLUT1 glucose transporter which increases glycolytic activity and accumulation of lactic acid. The protons generated by the synthesis of lactic acid are exported to the micro- environment where they contribute to acidification. There are two membrane-bound CAs that are associated with breast cancer: Carbonic anhydrase IX (CAIX) and carbonic anhydrase XII (CAXII). CAIX expression is associated with hypoxic regions of breast cancer tumors, metastatic disease, and poor patient prognosis. In contrast, CAXII expression is an indicator of good prognosis, despite catalyzing the same chemical reaction as CAIX. We hypothesize that CAIX is better able to regulate the pH of the microenvironment over that of CAXII which favors cancer cell survival. We are currently testing this hypothesis in cell lines and xenograft tumors.

Publications

Academic Articles
2024
Disruption of the Physical Interaction Between Carbonic Anhydrase IX and the Monocarboxylate Transporter 4 Impacts Lactate Transport in Breast Cancer Cells.
International journal of molecular sciences. 25(22) [DOI] 10.3390/ijms252211994. [PMID] 39596062.
2023
Effects of β-caryophyllene and oxygen availability on cholesterol and fatty acids in breast cancer cells.
PloS one. 18(3) [DOI] 10.1371/journal.pone.0281396. [PMID] 36893152.
2021
Inhibition of Carbonic Anhydrase Using SLC-149: Support for a Noncatalytic Function of CAIX in Breast Cancer.
Journal of medicinal chemistry. 64(3):1713-1724 [DOI] 10.1021/acs.jmedchem.0c02077. [PMID] 33523653.
2019
A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells.
The Biochemical journal. 476(10):1497-1513 [DOI] 10.1042/BCJ20190177. [PMID] 31072911.
2019
β-caryophyllene enhances the transcriptional upregulation of cholesterol biosynthesis in breast cancer cells.
Current topics in biochemical research. 20:1-16 [DOI] 10.31300/ctbr.20.2019.1-16. [PMID] 34733015.
2018
Biophysical, Biochemical, and Cell Based Approaches Used to Decipher the Role of Carbonic Anhydrases in Cancer and to Evaluate the Potency of Targeted Inhibitors.
International journal of medicinal chemistry. 2018 [DOI] 10.1155/2018/2906519. [PMID] 30112206.
2018
Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site.
Molecules (Basel, Switzerland). 23(5) [DOI] 10.3390/molecules23051045. [PMID] 29710858.
2018
Carbonic Anhydrases: Role in pH Control and Cancer.
Metabolites. 8(1) [DOI] 10.3390/metabo8010019. [PMID] 29495652.
2018
Differential expression and function of CAIX and CAXII in breast cancer: A comparison between tumorgraft models and cells.
PloS one. 13(7) [DOI] 10.1371/journal.pone.0199476. [PMID] 29965974.
2018
Selective inhibition of carbonic anhydrase IX over carbonic anhydrase XII in breast cancer cells using benzene sulfonamides: Disconnect between activity and growth inhibition.
PloS one. 13(11) [DOI] 10.1371/journal.pone.0207417. [PMID] 30452451.
2018
UFH-001 cells: A novel triple negative, CAIX-positive, human breast cancer model system.
Cancer biology & therapy. 19(7):598-608 [DOI] 10.1080/15384047.2018.1449612. [PMID] 29561695.
2017
Structure activity study of carbonic anhydrase IX: Selective inhibition with ureido-substituted benzenesulfonamides.
European journal of medicinal chemistry. 132:184-191 [DOI] 10.1016/j.ejmech.2017.03.026. [PMID] 28363153.
2016
The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.
Biochemistry. 55(33):4642-53 [DOI] 10.1021/acs.biochem.6b00243. [PMID] 27439028.
2015
Advances in Anti-Cancer Drug Development Targeting Carbonic Anhydrase IX and XII.
Topics in anti-cancer research. 5:3-42 [PMID] 30272043.
2015
Effects of acid-base variables and the role of carbonic anhydrase on oxalate secretion by the mouse intestine in vitro.
Physiological reports. 3(2) [DOI] 10.14814/phy2.12282. [PMID] 25716924.
2014
Overview of the carbonic anhydrase family.
Sub-cellular biochemistry. 75:3-5 [DOI] 10.1007/978-94-007-7359-2_1. [PMID] 24146371.
2014
Physiological functions of the alpha class of carbonic anhydrases.
Sub-cellular biochemistry. 75:9-30 [DOI] 10.1007/978-94-007-7359-2_2. [PMID] 24146372.
2012
Effect of Zinc On Carbonic Anhydrase Ix Activity in Mda-Mb-231 Breast Cancer Cells
The FASEB's Journal. 26
2012
Role of zinc in catalytic activity of carbonic anhydrase IX.
Archives of biochemistry and biophysics. 521(1-2):90-4 [DOI] 10.1016/j.abb.2012.03.017. [PMID] 22465027.
2011
Catalysis and pH control by membrane-associated carbonic anhydrase IX in MDA-MB-231 breast cancer cells.
The Journal of biological chemistry. 286(18):15789-96 [DOI] 10.1074/jbc.M110.188524. [PMID] 21454639.
2011
Role of hypoxia and EGF on expression, activity, localization and phosphorylation of carbonic anhydrase IX in MDA-MB-231 breast cancer cells.
Biochimica et biophysica acta. 1813(1):159-67 [DOI] 10.1016/j.bbamcr.2010.09.018. [PMID] 20920536.
2011
The promise of nanotechnology for solving clinical problems in breast cancer.
Journal of surgical oncology. 103(4):317-25 [DOI] 10.1002/jso.21698. [PMID] 21337565.
2010
Detecting extracellular carbonic anhydrase activity using membrane inlet mass spectrometry.
Analytical biochemistry. 403(1-2):74-8 [DOI] 10.1016/j.ab.2010.04.019. [PMID] 20417171.
2009
Antibody-specific detection of CAIX in breast and prostate cancers.
Biochemical and biophysical research communications. 386(3):488-92 [DOI] 10.1016/j.bbrc.2009.06.064. [PMID] 19538935.
2009
Expression and activity of carbonic anhydrase IX is associated with metabolic dysfunction in MDA-MB-231 breast cancer cells.
Cancer investigation. 27(6):613-23 [DOI] 10.1080/07357900802653464. [PMID] 19367501.
2009
Metabolic effects of different protein intakes after short term undernutrition in artificially reared infant rats.
Early human development. 85(1):41-9 [DOI] 10.1016/j.earlhumdev.2008.06.009. [PMID] 18650036.
2004
Glucose deprivation enhances targeting of GLUT1 to lipid rafts in 3T3-L1 adipocytes.
American journal of physiology. Endocrinology and metabolism. 286(4):E568-76 [PMID] 14665446.
2004
Soluble fibroin enhances insulin sensitivity and glucose metabolism in 3T3-L1 adipocytes.
The Journal of nutrition. 134(12):3257-63 [PMID] 15570022.
2002
Glycogen phosphorylase is activated in response to glucose deprivation but is not responsible for enhanced glucose transport activity in 3T3-L1 adipocytes.
Biochimica et biophysica acta. 1570(1):53-62 [PMID] 11960689.
2000
Alternative glycosylation of the insulin receptor prevents oligomerization and acquisition of insulin-dependent tyrosine kinase activity.
Biochimica et biophysica acta. 1499(1-2):74-84 [PMID] 11118640.
2000
Glucose deprivation does not affect GLUT1 targeting in 3T3-L1 adipocytes.
Biochemical and biophysical research communications. 273(3):859-64 [PMID] 10891337.
1999
Effect of alternative glycosylation on insulin receptor processing.
The Journal of biological chemistry. 274(32):22813-20 [PMID] 10428866.
1997
Development of insulin resistance in 3T3-L1 adipocytes.
The Journal of biological chemistry. 272(12):7759-64 [PMID] 9065437.
1997
Using magnetic beads to isolate inside-out GLUT1-containing vesicles from 3T3-L1 adipocyte plasma membranes.
Analytical biochemistry. 251(1):125-6 [PMID] 9300096.
1996
Differential regulation of GRP78 and GLUT1 expression in 3T3-L1 adipocytes.
Molecular and cellular biochemistry. 162(1):51-8 [PMID] 8905625.
1996
Glycogen: a carbohydrate source for GLUT-1 glycosylation during glucose deprivation of 3T3-L1 adipocytes.
The American journal of physiology. 270(4 Pt 1):E640-5 [PMID] 8928771.
1996
Insulin-stimulated glucose disposal: does adipose play a role?
Nutrition reviews. 54(10):329-31 [PMID] 9063024.
1996
Translocation of GLUT1 does not account for elevated glucose transport in glucose-deprived 3T3-L1 adipocytes.
The Journal of biological chemistry. 271(20):11806-9 [PMID] 8662621.
1995
Nutrient control of GLUT1 processing and turnover in 3T3-L1 adipocytes.
The Journal of biological chemistry. 270(20):12094-9 [PMID] 7744857.
1993
Effect of glucose deprivation of GLUT 1 expression in 3T3-L1 adipocytes.
The Journal of biological chemistry. 268(2):1320-5 [PMID] 7678253.
1992
Regulation of annexin I in adipogenesis: cAMP-independent action of methylisobutylxanthine.
The American journal of physiology. 262(1 Pt 1):C91-7 [PMID] 1370745.
1991
Annexin-I regulation in response to suckling and rat mammary cell differentiation.
Endocrinology. 128(3):1574-9 [PMID] 1825630.
1991
Protein-synthesis-dependent induction of annexin I by glucocorticoid.
The Biochemical journal. 275 ( Pt 2)(Pt 2):313-9 [PMID] 1827255.
1991
Role of receptor internalization in insulin signalling.
Advances in experimental medicine and biology. 293:215-25 [PMID] 1767732.
1990
Human relaxin inhibits division but not differentiation of 3T3-L1 cells.
Molecular and cellular endocrinology. 72(1):55-61 [PMID] 2272403.
1990
Uptake and binding of radiolabelled phenylarsine oxide in 3T3-L1 adipocytes.
The Biochemical journal. 269(3):589-95 [PMID] 2202293.
1989
Effect of phenylarsine oxide on fluid phase endocytosis: further evidence for activation of the glucose transporter.
Journal of cellular physiology. 141(3):467-74 [PMID] 2687296.
1989
Effect of phenylarsine oxide on protein synthesis in 3T3-L1 adipocytes.
Biochemical and biophysical research communications. 161(2):633-9 [PMID] 2735914.
1989
Effect of relaxin on differentiation of 3T3-L1 preadipocytes.
Endocrinology. 125(4):2049-55 [PMID] 2676478.
1987
Effect of phenylarsine oxide on insulin-dependent protein phosphorylation and glucose transport in 3T3-L1 adipocytes.
The Journal of biological chemistry. 262(20):9872-6 [PMID] 3298262.
1986
Identification and partial purification of the insulin-responsive glucose transporter from 3T3-L1 adipocytes.
Biochimica et biophysica acta. 885(3):317-26 [PMID] 3511974.
1986
Insulin stimulates fluid-phase endocytosis and exocytosis in 3T3-L1 adipocytes.
The Journal of biological chemistry. 261(9):3944-51 [PMID] 3512562.
1986
Insulin-dependent phosphorylation of the insulin receptor-protein kinase and activation of glucose transport in 3T3-L1 adipocytes.
The Journal of biological chemistry. 261(26):12272-81 [PMID] 3528154.
1985
Evidence for the involvement of vicinal sulfhydryl groups in insulin-activated hexose transport by 3T3-L1 adipocytes.
The Journal of biological chemistry. 260(5):2646-52 [PMID] 3882699.

Grants

Jul 2018 – Aug 2020
Enhancing the cytotoxic effects of ?-caryophyllene using statin drugs as a combinatorial therapy for the treatment of breast cancer
Role: Principal Investigator
Funding: OCALA ROYAL DAMES FOR CANCER RESEARCH
Apr 2013 – Mar 2019
Carbonic anhydrase and pH control in breast cancer cells
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Aug 2011 – Mar 2018
Small Cell Cancer Equipment and Research Competition
Role: Project Manager
Funding: UF FOUNDATION
Mar 2006 – May 2023
Davis Cancer Researach Equipment
Role: Project Manager
Funding: UF FOUNDATION

Contact Details

Phones:
Business:
(352) 226-2512
Emails:
Business:
sfrost@ufl.edu
Addresses:
Business Mailing:
PO Box 100245
GAINESVILLE FL 32610
Business Street:
R3216 ARB
GAINESVILLE FL 32611