D. Fernando Estrada PhD

D. Fernando Estrada

D. Fernando Estrada
PhD

Assistant Professor

Department of Biochemistry

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Metalloenzymes; Protein Function and Structure; Vitamins and Trace Nutrients

Contact Information
Rm 4222 JSMBS
955 Main Street
Department of Biochemistry
Buffalo, New York 14203
Phone: 716-829-2767
Fax: 716-829-2725
dfestrad@buffalo.edu



Professional Summary:

Cytochrome P450 enzymes are powerful catalysts that play integral roles in biochemical pathways throughout nature. In mammals, members of this class of enzyme serve a variety of functions that include drug metabolism, steroid biosynthesis and the activation and deactivation of vitamin D, to name a few. Cytochrome P450 enzymes are also heavily involved in bacterial and plant biochemistry.

The overall goal of our research is to use a combination of biochemical and biophysical tools to investigate structure and function in class I cytochrome P450 enzymes, thereby contributing toward an understanding of how this important class of enzymes work as well as informing the design of novel therapeutics.

This goal is divided between two efforts.

First, we are interested in characterizing the substrate and redox partner interactions of the enzymes CYP27B1 and CYP24A1, the P450s responsible for activating and deactivating vitamin D. Describing the interaction between CYP24A1 and vitamin D has the potential to illuminate how the vitamin D structure becomes modified at a particular site. This insight could impact the design of vitamin D analogs with benefits for an array of human health conditions, including bone density disorders, diabetes and chronic kidney disease (CKD).

A parallel effort in our group is a structural study of the enzyme CYP121 of Mycobacterium tuberculosis, the disease-causing pathogen in tuberculosis (TB). The resurgence of standard TB and the rise of drug-resistant forms of TB are quickly becoming a global pandemic, with TB claiming more lives worldwide in 2014 than HIV. CYP121 is essential for survival of the bacterium and thus has emerged as one of the more promising antitubercular drug targets.

Students and postdocs joining my lab will be exposed to a multidisciplinary set of research tools, including expression and purification of recombinant membrane proteins, nuclear magnetic resonance, protein X-ray crystallography and P450 ligand binding assays.

Education and Training:

  • PhD, Biochemistry & Biophysics, University of Kansas (2011)
  • BS, Biochemistry, Kansas State University (1999)
  • AAS, Biology, Dodge City Community College (1996)

Employment:

  • Adjunct Assistant Professor, Department of Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2021-present)
  • Assistant Professor of Biochemistry, Biochemistry, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2016-present)
  • Intelligence Officer, United State Army (1999–2006)

Awards and Honors:

  • Lila & Madison Self Graduate Fellowship (2007)
  • US Army Bronze Star for Meritorious Service (2003)

Grants and Sponsored Research:

  • September 2019–August 2024
    Structural regulation in mitochondrial vitamin-D and vitamin-A metabolizing cytochromes P450
    National Institute of General Medical Sciences
    Role: Principal Investigator
    $1,987,200
  • March 2015–July 2019
    Crystallographic and NMR studies of the human cytochrome P450 enzyme that inactivatesvitamin D
    National Institute of General Medical Sciences
    Role: Principal Investigator
    $939,995
  • November 2013–November 2015
    Ruth L. Kirschstein National Research Service Award; Application of solution NMR to membrane cytochrome P450 17A1
    National Institute of General Medical Sciences
    Role: Principal Investigator
    $122,264

Journal Articles:

See all (3 more)

Books and Book Chapters:

  • Estrada DF, Kumar A, Campomizzi CS, Jay N. (2021) Crystal structures of drug-metabolizing CYPs. In: Enzyme Kinetics in Drug Metabolism. Springer, 171-192.

Abstracts:

  • Campomizzi CS, Estrada DF. (2022) 19F-NMR shows that active site aromatic residues in CYP121 of Mycobacterial tuberculosis play a dual role in substrate interaction and protein structure. FASEB Journal, Experimental Biology 2022. Philadelphia, Pennsylvania (May), (492.8) Oral
  • Jay N, Duffy SR, Estrada DF. (2022) Characterization of a cleavable fusion of human CYP24A1 with Adrenodoxin reveals the variable role of hydrophobics in redox partner binding. FASEB Journal, Experimental Biology 2022. Philadelphia, Pennsylvania (May), (539.1) Oral
  • Jay N, Estrada DF. (2021) Adrenodoxin and substrate binding modulate the vitamin-D metabolizing human cytochrome P450 24A1. FASEB Journal, Experimental Biology 2021 (virtual). Buffalo, New York (May), (R2928) Poster
  • Kumar A, Estrada DF. (2021) Deciphering allosteric coupling between substrate binding and redox partner recognition in rat CYP24A1, a vitamin-D C-24 hydroxylase. FASEB Journal, Experimental Biology 2021 (virtual). Buffalo, New York (May), (R3549) Poster
  • Campomizzi CS, Estrada DF. (2021) 19F NMR illustrates novel aspects of Cytochrome P450 systems. FASEB Journal, Experimental Biology 2021 (virtual). Buffalo, New York (May), (R2327) Oral
  • Estrada DF. (2018) The cytochrome P450 24A1 interaction with Adrenodoxin modulates substrate binding and relies on species-variable recognition sites. FASEB Journal, Experimental Biology 2018. San Diego, California (May) Poster
  • Kumar A, Estrada DF. (2018) Mechanistic insight into species-specific redox partner interactions in the vitamin-D carbon-24 hydroxylase CYP24A1. FASEB Journal, Experimental Biology 2018. San Diego, California (May) Poster
  • Estrada DF, Tu Y. (2017) Preliminary investigation by NMR of the electron transfer complex between the vitamin-D metabolizing cytochrome P450 24A1 and Adrenodoxin. FASEB Journal, Experimental Biology 2017. Chicago, Illinois (May) Poster

Presentations:

  • "Non active-site regulation of CYP121A1; A therapeutic target from Mycobacterium tuberculosis" Department of Molecular Biosciences Seminar, University of Kansas (2022)
  • "More than a handshake: substrate and protein recognition events in the biochemistry of vitamin-D inactivation" International Conference on Organic, Medicinal and Pharmaceutical Chemistry-ICOMP-2022 (2022)
  • "A new role for CYP dimers: Understanding structural regulation for an essential CYP in Mycobacterium tuberculosis" Department Seminar, Chemistry Department, University of Texas at San Antonio (2021)
  • "Structural cross talk in vitamin-D metabolism" Experimental Biology Conference, ASPET Symposium (2021)
  • "Redox complex formation┬ámodulates function in a vitamin-D metabolizing cytochrome P450" Department Seminar, Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences (2020)
  • "A new role for CYP dimers" Department Seminar, School of Pharmacy and Pharmaceutical Sciences, Cardiff University (2020)
  • "Modes of structural regulation in Class I cytochrome P450 enzymes" Departmental Seminar; Case Western Reserve University; Department of Chemistry (2020)
  • "Novel structural regulation of vitamin-D metabolizing CYP24A1" Dr. John Omdahl Memorial Lecture; University of New Mexico School of Medicine; Department of Biochemistry and Molecular Biology (2019)
  • "Revisiting the sunshine vitamin: Novel structural regulation of the vitamin-D metabolizing enzyme CYP24A1" Departmental Seminar; Johns Hopkins University; Clinical Pharmacology Grand Rounds (2019)
  • "A new model of enzyme regulation in vitamin-D metabolism" Chemistry Department Seminar, Canisius College (2019)
  • "The secret handshake: specificity in mitochondrial P450-ferredoxin interactions" Chemistry Department Seminar, University at Buffalo (2018)
  • "The secret handshake: specificity in P450-redox partner interactions" Gordon Conference on Drug Metabolism; Gordon Research conference; Developments in drug metabolizing protein structures (2018)
See all (2 more)

Service Activities:

  • Journal of Inorganic Chemistry; Peer reviewer (2022)
  • CSTEP Research Symposium; Poster Judge (2022)
  • International Journal of Molecular Sciences; Peer reviewer (2022)
  • JSMBS Academic Appeals Committee; Member (2022–present)
  • ASBMB Undergraduate Poster Judge; Poster Judge (2022)
  • Frontiers in Genetics; Peer reviewer (2021)
  • Frontiers in Cellular and Infection Microbiology; Peer reviewer (2021)
  • ASPET Committee on Diversity, Equity, and Inclusion; Committee Member (2021–present)
  • MIRA-B Study Section; Standing Board Member (2021–present)
  • Pharmacology Research & Perspectives; Reviewing Editor (2021–present)
  • Graduate Affairs Committee; member (2020–present)
  • Anti-racism committee; member (2020–present)
  • International Journal of Virology and AIDS; Peer reviewer (2020)
  • Reviewer for KL2 Mentored Career Development Award; Reviewer (2020)
  • Xenobiotics and Nutrient Disposition (XNDA) Study Section; Ad hoc reviewer (2019–2020)
  • Search Committee, Chair for Department of Physiology and Biophysics; member (2019)
  • Senior Communications Officer, ASPET Drug Metabolism and Disposition Division; Senior Communications Officer (2019–2021)
  • PLOS ONE Journal; Peer reviewer (2019)
  • Adjudication and Grievance Committee; member (2019)
  • Special Emphasis Panel, Pratt Fellowship; Ad hoc reivewer (2019)
  • Frontiers in Pharmacology; Editorial Board Member (2019–present)
  • iSEED representative for JSMBS; iSEED representative for JSMBS (2019–present)
  • Secretary, Faculty Council Steering Committee; Secretary (2018–2020)
  • Biological Chemistry and Macromolecular Biophysics, NIH; ad hoc reviewer (2018)
  • Poster Judge, UB Postdoc Research Symposium; Poster Judge (2018)
  • ASBMB Undergraduate Poster Judge; Poster Judge (2018)
  • Faculty Search Committee; member (2018)
  • Biochemistry; Peer reviewer (2017)
  • Graduate School recruitment talk delivered to the Canisius College Women in Science club (2017)
  • Diversity Strategic Planning Committee; member (2017–present)
  • Basic Sciences Representative, Faculty Council Steering Committee; member (2017–2018)
  • Poster Judge, UB Postdoc Research Symposium; Poster Judge (2017)
  • Steroid Biochemistry and Molecular Biology; Peer review (2016)

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Contact Information

Rm 4222 JSMBS
955 Main Street
Department of Biochemistry
Buffalo, New York 14203
Phone: 716-829-2767
Fax: 716-829-2725
dfestrad@buffalo.edu