Brian K Law

Brian K Law, Ph.D.

Associate Professor

Department: MD-PHARMACOLOGY / THERAPEUTICS
Business Phone: (352) 273-9423
Business Email: bklaw@ufl.edu

Research Profile

Some of the Law Lab’s primary research interests revolves around cyclin-dependent kinases (Cdks) in mammary tumorigenesis and chromosomal instability, and Cdk regulation by the mTOR and TGFβ pathways. This research involves the use of novel models to understand how the activation of Cdks in the mammary gland causes tumor formation by dysregulation of cell proliferation and through genetic alterations that result from chromosomal instability. These models also provide systems for testing new therapeutic strategies, includinh non-ATP competitive Cdk inhibitors discovered in their laboratory and for targeting the upstream signaling pathways, such as the mTOR and TGFβ axes, that stimulate Cdk kinase activity.

The mechanisms promoting breast cancer invasion and metastasisE-cadherin are the primary barriers preventing the invasion and metastasis of human carcinomas; therefore, their functions must be abrogated in epithelial cancers in order for tumor dissemination to occur. E-cadherin expression can be blocked by epigenetic silencing, but the lab’s results indicate that the loss of the E-cadherin protein function is highly prevalent among the most aggressive breast cancers. The Law Lab has discovered that the protein, Cub Domain-Containing Protein 1 (CDCP1), which has been implicated in tumor invasion and metastasis, is a novel E-cadherin-associated protein. Ongoing studies focus on determining how CDCP1 controls cell-cell adhesion through its association with Cadherins, Catenins, cytoskeletal proteins, and Matrix Metalloproteinases.

Open Researcher and Contributor ID (ORCID)

0000-0002-8411-6531

Publications

2019
A metabolic switch in proteasome inhibitor-resistant multiple myeloma ensures higher mitochondrial metabolism, protein folding and sphingomyelin synthesis.
Haematologica. 104(9):e415-e419 [DOI] 10.3324/haematol.2018.207704. [PMID] 30792209.
2019
A novel proteotoxic combination therapy for EGFR+ and HER2+ cancers.
Oncogene. 38(22):4264-4282 [DOI] 10.1038/s41388-019-0717-6.
2019
ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.
European journal of medicinal chemistry. 161:456-467 [DOI] 10.1016/j.ejmech.2018.10.052. [PMID] 30384048.
2019
Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway.
Cell Death Discovery. 5 [DOI] 10.1038/s41420-019-0228-9. [PMID] 31839995.
2018
Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers.
Aging cell. 17(4) [DOI] 10.1111/acel.12761. [PMID] 29774638.
2018
The unfolded protein response as a target for anticancer therapeutics.
Critical reviews in oncology/hematology. 127:66-79 [DOI] 10.1016/j.critrevonc.2018.05.003. [PMID] 29891114.
2017
Disulfide bond disrupting agents activate the unfolded protein response in EGFR- and HER2-positive breast tumor cells.
Oncotarget. 8(17):28971-28989 [DOI] 10.18632/oncotarget.15952. [PMID] 28423644.
2017
Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.
Journal of natural products. 80(11):2969-2986 [DOI] 10.1021/acs.jnatprod.7b00551. [PMID] 29087712.
2017
Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer.
Marine drugs. 15(9) [DOI] 10.3390/md15090290. [PMID] 28926939.
2017
NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.
Oncotarget. 8(34):57246-57264 [DOI] 10.18632/oncotarget.19778. [PMID] 28915668.
2016
CUB domain-containing protein 1 and the epidermal growth factor receptor cooperate to induce cell detachment.
Breast cancer research : BCR. 18(1) [DOI] 10.1186/s13058-016-0741-1. [PMID] 27495374.
2016
Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells.
The Journal of clinical investigation. 126(11):4174-4186 [DOI] 10.1172/JCI86623. [PMID] 27721239.
2016
Interaction between APC and Fen1 during breast carcinogenesis.
DNA repair. 41:54-62 [DOI] 10.1016/j.dnarep.2016.04.003. [PMID] 27088617.
2016
Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.
Cell death and differentiation. 23(2):279-90 [DOI] 10.1038/cdd.2015.96. [PMID] 26184910.
2015
Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics.
Molecular pharmacology. 88(5):846-52 [DOI] 10.1124/mol.115.099325. [PMID] 26018905.
2015
Novel agents that downregulate EGFR, HER2, and HER3 in parallel.
Oncotarget. 6(12):10445-59 [PMID] 25865227.
View on: PubMed
2015
NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage, Senescence and Apoptosis in Colorectal Cancer Cells.
PloS one. 10(5) [DOI] 10.1371/journal.pone.0123808. [PMID] 25933036.
2015
Targeted Inhibition of PAI-1 Activity Impairs Epithelial Migration and Wound Closure Following Cutaneous Injury.
Advances in wound care. 4(6):321-328 [PMID] 26029482.
View on: PubMed
2015
VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner.
Cancer letters. 360(1):60-7 [DOI] 10.1016/j.canlet.2015.02.005. [PMID] 25676691.
2014
A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.
Autophagy. 10(11):2021-35 [DOI] 10.4161/auto.32229. [PMID] 25483883.
2014
SERPINE1: A Molecular Switch in the Proliferation-Migration Dichotomy in Wound-“Activated” Keratinocytes.
Advances in wound care. 3(3):281-290 [PMID] 24669362.
View on: PubMed
2014
Signaling mechanisms that suppress the cytostatic actions of rapamycin.
PloS one. 9(6) [DOI] 10.1371/journal.pone.0099927. [PMID] 24927123.
2014
The basic helix-loop-helix/leucine zipper transcription factor USF2 integrates serum-induced PAI-1 expression and keratinocyte growth.
Journal of cellular biochemistry. 115(10):1840-7 [DOI] 10.1002/jcb.24861. [PMID] 24905330.
2013
Assembly, activation, and substrate specificity of cyclin D1/Cdk2 complexes.
Biochemistry. 52(20):3489-501 [DOI] 10.1021/bi400047u. [PMID] 23627734.
2013
Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints.
Journal of cell science. 126(Pt 5):1207-17 [DOI] 10.1242/jcs.117382. [PMID] 23321641.
2013
Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development.
Cancer letters. 332(1):120-9 [DOI] 10.1016/j.canlet.2012.11.016. [PMID] 23196055.
2013
Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms.
Oncogene. 32(10):1316-29 [DOI] 10.1038/onc.2012.138. [PMID] 22543582.
2013
Small-Molecule Inhibitors of Acetyltransferase P300 Identified By High-Throughput Screening Are Potent Anticancer Agents (Vol 12, Pg 610, 2013)
Molecular Cancer Therapeutics. 12(8):1688-1688 [DOI] 10.1158/1535-7163.MCT-13-0441.
2013
Small-molecule inhibitors of acetyltransferase p300 identified by high-throughput screening are potent anticancer agents.
Molecular cancer therapeutics. 12(5):610-20 [DOI] 10.1158/1535-7163.MCT-12-0930. [PMID] 23625935.
2013
The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition.
The Journal of biological chemistry. 288(38):27680-27691 [DOI] 10.1074/jbc.M113.482349. [PMID] 23928305.
2012
An in vivo model of epithelial to mesenchymal transition reveals a mitogenic switch.
Cancer letters. 326(2):183-90 [DOI] 10.1016/j.canlet.2012.08.013. [PMID] 22906417.
2012
TGF-beta antiproliferative effects in tumor suppression.
Frontiers in bioscience (Scholar edition). 4:749-66 [PMID] 22202088.
View on: PubMed
2011
In Pursuit of New Anti-Angiogenic Therapies for Cancer Treatment
Meditsinskaia parazitologiia i parazitarnye bolezni. 16(5):803-814 [DOI] 10.2741/3721. [PMID] 3721.
2011
In pursuit of new anti-angiogenic therapies for cancer treatment.
Frontiers in bioscience (Landmark edition). 16:803-14 [PMID] 21196204.
View on: PubMed
2011
αB-crystallin, an effector of unfolded protein response, confers anti-VEGF resistance to breast cancer via maintenance of intracrine VEGF in endothelial cells.
Molecular cancer research : MCR. 9(12):1632-43 [DOI] 10.1158/1541-7786.MCR-11-0327. [PMID] 21984182.
2010
Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor.
The Journal of pharmacology and experimental therapeutics. 335(2):351-61 [DOI] 10.1124/jpet.110.172387. [PMID] 20739454.
2010
Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF-kappaB using in silico molecular docking.
Cancer letters. 291(2):217-24 [DOI] 10.1016/j.canlet.2009.10.015. [PMID] 19910110.
2010
Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition.
Oncogene. 29(35):4896-904 [DOI] 10.1038/onc.2010.234. [PMID] 20562920.
2010
The B56gamma3 regulatory subunit of protein phosphatase 2A (PP2A) regulates S phase-specific nuclear accumulation of PP2A and the G1 to S transition.
The Journal of biological chemistry. 285(28):21567-80 [DOI] 10.1074/jbc.M109.094953. [PMID] 20448040.
2009
A novel class of cyclin-dependent kinase inhibitors identified by molecular docking act through a unique mechanism.
The Journal of biological chemistry. 284(43):29945-55 [DOI] 10.1074/jbc.M109.055251. [PMID] 19710018.
2009
Amino acid Asp181 of 5′-flap endonuclease 1 is a useful target for chemotherapeutic development.
Biochemistry. 48(42):9952-8 [DOI] 10.1021/bi9010754. [PMID] 19769410.
2009
Apratoxin a reversibly inhibits the secretory pathway by preventing cotranslational translocation.
Molecular pharmacology. 76(1):91-104 [DOI] 10.1124/mol.109.056085. [PMID] 19403701.
2009
Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest.
Differentiation; research in biological diversity. 78(1):35-44 [DOI] 10.1016/j.diff.2009.04.001. [PMID] 19427096.
2009
Identification of Compounds That Enhance and Suppress Autophagy
Autophagy. 5:910-911
2009
Identification of genes, including the gene encoding p27Kip1, regulated by serine 276 phosphorylation of the p65 subunit of NF-kappaB.
Cancer letters. 275(1):139-49 [DOI] 10.1016/j.canlet.2008.10.007. [PMID] 19038492.
2008
Identification of novel Smad2 and Smad3 associated proteins in response to TGF-beta1.
Journal of cellular biochemistry. 105(2):596-611 [DOI] 10.1002/jcb.21860. [PMID] 18729074.
2008
Lessons From the First Comprehensive Molecular Characterization of Cell Cycle Control in Rodent Insulinoma Cell Lines
Diabetes. 57(11):3056-3068 [DOI] 10.2337/db08-0393. [PMID] 18650366.
2008
Mammary tumors initiated by constitutive Cdk2 activation contain an invasive basal-like component.
Neoplasia (New York, N.Y.). 10(11):1240-52 [PMID] 18953433.
View on: PubMed
2008
Tumors Initiated By Constitutive Cdk2 Activation Contain An Invasive Basal Component
Virchows Archiv. 452:S147-S148
2007
Identification of a PP2A interacting protein that functions as a negative regulator of phosphatase activity in the ATM/ATR signaling pathway
Oncogene. 26:6021-6030
2007
Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression.
Cancer research. 67(7):3135-44 [PMID] 17409420.
View on: PubMed
2006
Cellular Mechanism Through Which Parathyroid Hormone-Related Protein Induces Proliferation in Arterial Smooth Muscle Cells
. 99:933-942
2006
Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes.
Cancer research. 66(2):1070-80 [PMID] 16424043.
View on: PubMed
2006
Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA stability associated with invasiveness by autocrine and paracrine transforming growth factor-beta.
The Journal of biological chemistry. 281(45):33971-81 [PMID] 16959768.
View on: PubMed
2005
Rapamycin: an anti-cancer immunosuppressant?
Critical reviews in oncology/hematology. 56(1):47-60 [PMID] 16039868.
View on: PubMed
2005
Signaling Cross-talk between Insulin-like Growth Factor Binding Protein-3 (IGFBP3) and Transforming Growth Factor-ß (TGFß)
Journal of Molecular Endocrinology. 34:723-737
2004
Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro.
Neoplasia (New York, N.Y.). 6(5):603-10 [PMID] 15548370.
View on: PubMed
2004
Transforming growth factor-beta induces Cdk2 relocalization to the cytoplasm coincident with dephosphorylation of retinoblastoma tumor suppressor protein.
Breast cancer research : BCR. 6(2):R130-9 [PMID] 14979923.
View on: PubMed
2003
Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line.
Breast cancer research : BCR. 5(6):R187-98 [PMID] 14580254.
View on: PubMed
2002
Rapamycin potentiates transforming growth factor beta-induced growth arrest in nontransformed, oncogene-transformed, and human cancer cells.
Molecular and cellular biology. 22(23):8184-98 [PMID] 12417722.
View on: PubMed
Identification of the Molecular Targets of Disulfide Bond Disrupting Agents
. [DOI] 10.1101/2021.01.13.426390.
Mechanistic Elucidation of the Antitumor Properties of a Novel Death Receptor 5 Activator
. [DOI] 10.1101/700906.

Grants

Jul 2020 ACTIVE
Regulation of Death Receptor 5 folding and apoptotic signaling by AGR2
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Jul 2020 ACTIVE
Tranexamic Class Antagonists (TXCAs)
Role: Co-Investigator
Funding: TRANEXAMIC TECHNOLOGIES
Aug 2019 ACTIVE
Tranexamic Acid Activity Against Melanoma and Breast Cancer
Role: Principal Investigator
Funding: TRANEXAMIC TECHNOLOGIES
Jul 2019 – Dec 2020
Dual mechanisms of DDA antitumor activity: Induction of tumor cell apoptosis and vascular disruption
Role: Principal Investigator
Funding: FL BREAST CANCER FOU
Jul 2018 – Dec 2020
A new approach for eradicating metastatic, drug-resistant breast cancers
Role: Principal Investigator
Funding: OCALA ROYAL DAMES FOR CANCER RESEARCH
Feb 2018 – May 2019
Synthetic lethal strategy for killing EGFR+/HER2+ cancers
Role: Principal Investigator
Funding: FL BREAST CANCER FOU
Jul 2015 ACTIVE
Florida Academic Cancer Center Alliance Seed Grants
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Jun 2015 – Sep 2019
Novel agents that simultaneously downregulate Her2, EGFR, and Her3
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Feb 2015 ACTIVE
UF Health Cancer Center Pilot Project Grants funded through the Florida Consortium of National Cancer Institute Centers Program
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Feb 2015 – Jan 2016
CDCP1 as a therapeutic target in the dissemination of a
Role: Principal Investigator
Funding: UF FOU
Jul 2014 – Jun 2021
Martens-Maren Chair Fund
Role: Project Manager
Funding: **UF FOU UNRESTRICTED DONATION
Dec 2013 – Nov 2015
Chemistry and Biology of Apratoxins
Role: Project Manager
Funding: FL DEPT OF HLTH BANKHEAD-COLEY CANCER RE
Oct 2013 – Oct 2016
Nuovo Biologics Testing
Role: Principal Investigator
Funding: NUOVO BIOLOGICS
Mar 2013 – Aug 2019
Novel Targeted Anticancer Agents from Marine Cyanobacteria
Role: Project Manager
Funding: NATL INST OF HLTH NCI
Jul 2006 – Dec 2020
21st Century Research & Economic Development Investment Program (REDIP)
Role: Project Manager
Funding: STATE UNIV SYS OF FL BOARD OF GOVERNORS

Patents

Published April 2017
Novel Small Molecule Anticancer Agents
#US-2017-0240570-A1
Issued November 2016
Combination Compositions and Methods of Treatment
#9,492,434
Issued October 2013
Cyclin Dependent Kinase Inhibitors
#8,569,356
Published February 2012
Methods and Compositions for the Treatment of Cancers and Pathogenic Infections
#US-2012-0141491-A1

Teaching Profile

Courses Taught
2019-2021
GMS6551 Fundamentals of Medical Pharmacology and Therapeutics
2019-2021
GMS6540 GMS 6840 Medical Pharmacology and Therapeutics IV: Cancer, Antimicrobial and Antiparasitic Agents
2019-2021
GMS6520 Medical Pharmacology and Therapeutics I: The Nervous System
2019-2021
GMS6531 Medical Pharmacology and Therapeutics III: Endocrine, Musculoskeletal and Reproductive Systems
2018-2021
GMS6560 Molecules to Man: Past, Present and Future Therapeutic Strategies for Disease
2019-2021
GMS6530 Medical Pharmacology and Therapeutics II: Cardiovascular, Renal and Respiratory Systems
2020-2021
PAS5026 Pharmacotherapeu 2
2013-2014,2016-2021
GMS6001 Fundamentals of Biomedical Sciences I
2016-2021
GMS6847 Translational Research and Therapeutics: Bench, Bedside, Community, & Policy
2020-2021
GMS6691 Special Topics in Cell Biology and Anatomy
2011-2013,2015-2021
GMS6009 Principles of Drug Action and Therapeutics
2011-2021
DEN6262 Prin of Pharmacology
2014-2015,2017-2021
GMS6065 Fundamentals of Cancer Biology
2016-2018,2020-2021
GMS6064 Tumor Biology
2018
GMS7980 Research for Doctoral Dissertation
2018
CHM7979 Advanced Research
2018
GMS7979 Advanced Research
2015,2018
BMS6638C Kidney & Urinary Tract
2018
BMS6300 Fund Micro and Immuno
2013,2015-2017
GMS6051 Signal Transduction
2014,2016
MDU4002 Introduction to Medical Science Seminar 2
2016
GMS6644 Apoptosis
2013-2014
BMS6031 Foundations of Med
2021
GMS6552 Cell Signaling & Therapeutics
2021
GMS6504 Advanced Medical Pharmacology

Contact Details

Phones:
Business:
(352) 273-9423
Emails:
Business:
bklaw@ufl.edu