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Gregg Fields, Ph.D. - Florida Atlantic University. Boca Raton, FL, US

Gregg Fields, Ph.D.

Executive Director | Florida Atlantic University


Gregg Fields uses chemistry to answer biological questions, many of which assist in the diagnosis and treatment of major diseases.






FAU Scientist Gregg Fields, Ph.D.: The Search for Novel Cancer Inhibitors FAU Faculty Vignette – Gregg Fields, Ph.D.




Gregg Fields applies chemistry in novel ways to answer important biological questions, many of which assist in the diagnosis and treatment of major diseases, such as multiple sclerosis, arthritis and cancer.

Fields is a fellow of the National Academy of Inventors and a fellow of the American Association for the Advancement of Science. He is a renowned researcher who holds 7 U.S. patents. The technology developed by Fields has resulted in three commercial products, currently sold by five different companies. He has authored or co-authored more than 300 scientific publications and has presented more than 200 invited lectures.

Areas of Expertise (7)

Extracellular Matrix Biochemistry

Matrix Metalloproteinase


Drug Discovery

Protein Biochemistry

Chemical Biology

Solid Phase Synthesis

Accomplishments (8)

Elected Fellow, American Association for the Advancement of Science (AAAS)


Distinguished Chair of Metalloproteinase and Multiple Sclerosis Research, TPIMS


Elected Fellow, National Academy of Inventors


Arthritis & Chronic Pain Research Institute Lecturer, University of Florence, Italy


Robert A. Welch Foundation Distinguished University Chair in Chemistry, University of Texas Health Science Center at San Antonio,


National Institutes of Health Research Career Development Award


Association of Biomolecular Resource Facilities Excellence Award in Peptide Synthesis Research


McKnight-Land Grant Professorship

University of Minnesota, 1993-1995

Education (3)

University of California, San Francisco - School of Medicine: Postdoctoral Scholar, Pharmaceutical Chemistry 1991

Florida State University: Ph.D., Chemistry 1988

University of Florida: B.S., Chemistry 1982

Affiliations (3)

  • American Association for the Advancement of Science : Member
  • Center for Molecular Biology & Biotechnology, FAU : Director
  • Journal of Cellular Physiology : Editor-in-Chief

Selected Media Appearances (4)

'There's hope:' Delray Medical, FAU progress in Alzheimer's research using new technology

CBS12  online


“The process does take several hours, at least three hours to do this,” explained FAU Dr. Gregg Fields on Friday. After the treatment is done, researchers like Dr. Fields look at scans and blood samples collected to see if it’s even working.

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Learn how FAU researchers are battling cancer at free town hall Wednesday

The Palm Beach Post  online


Like so many medical science researchers, Florida Atlantic University chemistry and biochemistry professor Dr. Gregg Fields has a personal connection to the disease he has dedicated his life to studying. “All four of my grandparents died of cancer,” says Fields. “Both of my parents were cancer survivors (and my 93-year-old dad is still with us!) and my sister is a breast cancer survivor. So far, my brother and I are the only ones who have been spared.”

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FAU Professor Gregg Fields Named NAI Fellow

University Press  online


Gregg Fields, the chair for FAU’s Department of Chemistry and Biochemistry and the director of the Center of Molecular Biology and Biotechnology, has just been named a National Academy of Inventors Fellow. The NAI Fellows program has “414 Fellows worldwide representing more than 150 prestigious universities and governmental and non-profit research institutions,” as stated on their website. All of these inventors have patents – at least one is required for nomination – with the United States Patent and Trademark Office, and together the 414 Fellows amass nearly 14,000 patents. Fields will be joining the likes of Jay S. Walker, founder of Priceline and Curtis Carlson, president and CEO of SRI International.

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UT Health Science Center Pockets $11.6M to Study Heart Failure Markers

Genetic Engineering & Biotechnology News  online


Goal is to identify extracellular matrix peptides that can be used as predictors. A blood test to diagnose which heart attack survivors will suffer heart failure is the goal of a new five-year, $11.6 million contract to the UT Health Science Center San Antonio (UTSA) from the National Heart, Lung, and Blood Institute (NHLBI).

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Selected Articles (9)

A collagen glucosyltransferase drives lung adenocarcinoma progression in mice

Communications Biology

uo HF, Bota-Rabassedas N, Terajima M, Leticia Rodriguez B, Gibbons DL, Chen Y, Banerjee P, Tsai CL, Tan X, Liu X, Yu J, Tokmina-Roszyk M, Stawikowska R, Fields GB, Miller MD, Wang X, Lee J, Dalby KN, Creighton CJ, Phillips GN Jr, Tainer JA, Yamauchi M, Kurie JM

2021 Cancer cells are a major source of enzymes that modify collagen to create a stiff, fibrotic tumor stroma. High collagen lysyl hydroxylase 2 (LH2) expression promotes metastasis and is correlated with shorter survival in lung adenocarcinoma (LUAD) and other tumor types. LH2 hydroxylates lysine (Lys) residues on fibrillar collagen's amino- and carboxy-terminal telopeptides to create stable collagen cross-links. Here, we show that electrostatic interactions between the LH domain active site and collagen determine the unique telopeptidyl lysyl hydroxylase (tLH) activity of LH2. However, CRISPR/Cas-9-mediated inactivation of tLH activity does not fully recapitulate the inhibitory effect of LH2 knock out on LUAD growth and metastasis in mice, suggesting that LH2 drives LUAD progression, in part, through a tLH-independent mechanism. Protein homology modeling and biochemical studies identify an LH2 isoform (LH2b) that has previously undetected collagen galactosylhydroxylysyl glucosyltransferase (GGT) activity determined by a loop that enhances UDP-glucose-binding in the GLT active site and is encoded by alternatively spliced exon 13 A. CRISPR/Cas-9-mediated deletion of exon 13 A sharply reduces the growth and metastasis of LH2b-expressing LUADs in mice. These findings identify a previously unrecognized collagen GGT activity that drives LUAD progression.

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Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma-Induced Osteolysis and Reduces Overall Survival

Cancer Research

Lo CH, Shay G, McGuire JJ, Li T, Shain KH, Choi JY, Fuerst R, Roush WR, Knapinska AM, Fields GB, Lynch CC

2021 Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen-rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can drive progression of the disease. Matrix metalloproteinase-13 (MMP13) is a collagenase expressed predominantly in the skeleton by mesenchymal stromal cells (MSC) and MSC-derived osteoblasts. Histochemical analysis of human multiple myeloma specimens also demonstrated that MMP13 largely localizes to the stromal compartment compared with CD138+ myeloma cells. In this study, we further identified that multiple myeloma induces MMP13 expression in bone stromal cells. Because of its ability to degrade type I collagen, we examined whether bone stromal-derived MMP13 contributed to myeloma progression. Multiple myeloma cells were inoculated into wild-type or MMP13-null mice. In independent in vivo studies, MMP13-null mice demonstrated significantly higher overall survival rates and lower levels of bone destruction compared with wild-type controls. Unexpectedly, no differences in type I collagen processing between the groups were observed. Ex vivo stromal coculture assays showed reduced formation and activity in MMP13-null osteoclasts. Analysis of soluble factors from wild-type and MMP13-null MSCs revealed decreased bioavailability of various osteoclastogenic factors including CXCL7. CXCL7 was identified as a novel MMP13 substrate and regulator of osteoclastogenesis. Underscoring the importance of host MMP13 catalytic activity in multiple myeloma progression, we demonstrate the in vivo efficacy of a novel and highly selective MMP13 inhibitor that provides a translational opportunity for the treatment of this incurable disease. SIGNIFICANCE: Genetic and pharmacologic approaches show that bone stromal-derived MMP13 catalytic activity is critical for osteoclastogenesis, bone destruction, and disease progression.

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Matrix Metalloproteinase 13 Inhibitors for Modulation of Osteoclastogenesis: Enhancement of Solubility and Stability


Knapinska AM, Singh C, Drotleff G, Blanco D, Chai C, Schwab J, Herd A, Fields GB

2021 Matrix metalloproteinase 13 (MMP-13) activity has been correlated to breast cancer bone metastasis. It has been proposed that MMP-13 contributes to bone metastasis through the promotion of osteoclastogenesis. To explore the mechanisms of MMP-13 action, we previously described a highly efficacious and selective MMP-13 inhibitor, RF036. Unfortunately, further pursuit of RF036 as a probe of MMP-13 in vitro and in vivo activities was not practical due to the limited solubility and stability of the inhibitor. Our new study has explored replacing the RF036 backbone sulfur atom and terminal methyl group to create inhibitors with more favorable pharmacokinetic properties. One compound, designated inhibitor 3, in which the backbone sulfur and terminal methyl group of RF036 were replaced by nitrogen and oxetane, respectively, had comparable activity, selectivity, and membrane permeability to RF036, while exhibiting greatly enhanced solubility and stability. Inhibitor 3 effectively inhibited MMP-13-mediated osteoclastogenesis but spared collagenolysis, and thus represents a next-generation MMP-13 probe applicable for in vivo studies of breast cancer metastasis.

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A Novel Probe for Spliceosomal Proteins that Induces Autophagy and Death of Melanoma Cells Reveals New Targets for Melanoma Drug Discovery

Cellular Physiology and Biochemistry

Palrasu M, Knapinska AM, Diez J, Smith L, LaVoi T, Giulianotti M, Houghten RA, Fields GB, Minond D

2019 Background/aims: Despite recent advances in melanoma drug discovery, the average overall survival of patients with late stage metastatic melanoma is approximately 3 years, suggesting a need for approaches that identify new melanoma targets. We have previously reported a discovery of novel anti-melanoma compound 2155-14 (Onwuha-Ekpete et al., J Med Chem. 2014 Feb 27; 57(4):1599-608). In the report presented herein we aim to identify its target(s) and mechanism of action. Methods: We utilized biotinylated analog of 2155-14 to pull down its targets from melanoma cells. Proteomics in combination with western blot were used to identify the targets. Mechanism of action of 2155-14 was determined using flow cytometry, RT-PCR, microscopy, western blot, and enzymatic activity assays. Where applicable, one-way analysis of variance (ANOVA) was used followed by Dunnett post hoc test. Results: In the present study, we identified ATP-dependent RNA helicase DDX1 and heterogeneous nuclear ribonucleoproteins (hnRNPs) H1, H2 and A2/B1 as targets of anti-melanoma compound 215514. To the best of our knowledge, this is a first report suggesting that these proteins could be targeted for melanoma therapy. Mechanistic investigations showed that 2155-14 induces ER stress leading to potentiation of basal autophagy resulting in melanoma cell death in BRAF and NRAS mutated melanoma cells. Conclusion: Identification of mode of action of 2155-14 may provide insight into novel therapies against a broad range of melanoma subtypes. These studies were enabled by the novel probe derived from a mixture-based library, an important class of chemical biology tools for discovering novel targets.

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The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma


Gregg B Fields

2019 The pursuit of matrix metalloproteinase (MMP) inhibitors began in earnest over three decades ago. Initial clinical trials were disappointing, resulting in a negative view of MMPs as therapeutic targets. As a better understanding of MMP biology and inhibitor pharmacokinetic properties emerged, it became clear that initial MMP inhibitor clinical trials were held prematurely. Further complicating matters were problematic conclusions drawn from animal model studies. The most recent generation of MMP inhibitors have desirable selectivities and improved pharmacokinetics, resulting in improved toxicity profiles. Application of selective MMP inhibitors led to the conclusion that MMP-2, MMP-9, MMP-13, and MT1-MMP are not involved in musculoskeletal syndrome, a common side effect observed with broad spectrum MMP inhibitors. Specific activities within a single MMP can now be inhibited. Better definition of the roles of MMPs in immunological responses and inflammation will help inform clinic trials, and multiple studies indicate that modulating MMP activity can improve immunotherapy. There is a U.S. Food and Drug Administration (FDA)-approved MMP inhibitor for periodontal disease, and several MMP inhibitors are in clinic trials, targeting a variety of maladies including gastric cancer, diabetic foot ulcers, and multiple sclerosis. It is clearly time to move on from the dogma of viewing MMP inhibition as intractable.

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MT1-MMP Binds Membranes by Opposite Tips of Its β Propeller to Position It for Pericellular Proteolysis


Marcink TC, Simoncic JA, An B, Knapinska AM, Fulcher YG, Akkaladevi N, Fields GB, Van Doren SR

2019 Critical to migration of tumor cells and endothelial cells is the proteolytic attack of membrane type 1 matrix metalloproteinase (MT1-MMP) upon collagen, growth factors, and receptors at cell surfaces. Lipid bilayer interactions of the substrate-binding hemopexin-like (HPX) domain of MT1-MMP were investigated by paramagnetic nuclear magnetic resonance relaxation enhancements (PREs), fluorescence, and mutagenesis. The HPX domain binds bilayers by blades II and IV on opposite sides of its β propeller fold. The EPGYPK sequence protruding from both blades inserts among phospholipid head groups in PRE-restrained molecular dynamics simulations. Bilayer binding to either blade II or IV exposes the CD44 binding site in blade I. Bilayer association with blade IV allows the collagen triple helix to bind without obstruction. Indeed, vesicles enhance proteolysis of collagen triple-helical substrates by the ectodomain of MT1-MMP. Hypothesized side-by-side MT1-MMP homodimerization would allow binding of bilayers, collagen, CD44, and head-to-tail oligomerization.

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Matrix Metalloproteinase Inhibition by Heterotrimeric Triple‐Helical Peptide Transition State Analogues

Wiley Online Library

Dr. Manishabrata Bhowmick Roma Stawikowska Dorota Tokmina‐Roszyk Prof. Gregg B. Fields

2015 Matrix metalloproteinases (MMPs) have been implicated in numerous pathologies. An overall lack of selectivity has rendered active‐site‐targeted MMP inhibitors problematic. The present study describes MMP inhibitors that function by binding both secondary binding sites (exosites) and the active site. Heterotrimeric triple‐helical peptide transition‐state analogue inhibitors (THPIs) were assembled utilizing click chemistry. Three different heterotrimers were constructed, allowing for the inhibitory phosphinate moiety to be present uniquely in the leading, middle, or trailing strand of the triple helix. All heterotrimeric constructs had sufficient thermally stability to warrant analysis as inhibitors. The heterotrimeric THPIs were effective against MMP‐13 and MT1‐MMP, with Ki values spanning 100–400 nM. Unlike homotrimeric THPIs, the heterotrimeric THPIs offered complete selectivity between MT1‐MMP and MMP‐1. Exosite‐based approaches such as this provide inhibitors with desired MMP selectivities.

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Novel Pyrrolidine Diketopiperazines Selectively Inhibit Melanoma Cells via Induction of Late-Onset Apoptosis

Journal of Medicinal Chemistry

Lillian Onwuha-Ekpete, Lisa Tack, Anna Knapinska, Lyndsay Smith, Gaurav Kaushik, Travis LaVoi, Marc Giulianotti, Richard A. Houghten, Gregg B. Fields, and Dmitriy Minond

2014 A common liability of cancer drugs is toxicity to noncancerous cells. Thus, molecules are needed that are potent toward cancer cells while sparing healthy cells. The cost of traditional cell-based HTS is dictated by the library size, which is typically in the hundreds of thousands of individual compounds. Mixture-based combinatorial libraries offer a cost-effective alternative to single-compound libraries while eliminating the need for molecular target validation. Presently, lung cancer and melanoma cells were screened in parallel with healthy cells using a mixture-based library. A novel class of compounds was discovered that selectively inhibited melanoma cell growth via apoptosis with submicromolar potency while sparing healthy cells. Additionally, the cost of screening and biological follow-up experiments was significantly lower than in typical HTS. Our findings suggest that mixture-based phenotypic HTS can significantly reduce cost and hit-to-lead time while yielding novel compounds with promising pharmacology.

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Structural Basis for Matrix Metalloproteinase 1-Catalyzed Collagenolysis

Journal of the American Chemical Society

Ivano Bertini, Marco Fragai, Claudio Luchinat, Maxime Melikian, Mirco Toccafondi, Janelle L. Lauer, and Gregg B. Fields

2011 The proteolysis of collagen triple-helical structure (collagenolysis) is a poorly understood yet critical physiological process. Presently, matrix metalloproteinase 1 (MMP-1) and collagen triple-helical peptide models have been utilized to characterize the events and calculate the energetics of collagenolysis via NMR spectroscopic analysis of 12 enzyme–substrate complexes. The triple-helix is bound initially by the MMP-1 hemopexin-like (HPX) domain via a four amino acid stretch (analogous to type I collagen residues 782–785). The triple-helix is then presented to the MMP-1 catalytic (CAT) domain in a distinct orientation. The HPX and CAT domains are rotated with respect to one another compared with the X-ray “closed” conformation of MMP-1. Back-rotation of the CAT and HPX domains to the X-ray closed conformation releases one chain out of the triple-helix, and this chain is properly positioned in the CAT domain active site for subsequent hydrolysis. The aforementioned steps provide a detailed, experimentally derived, and energetically favorable collagenolytic mechanism, as well as significant insight into the roles of distinct domains in extracellular protease function.

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