May 16, 2019

Cancer Institute Member Spotlight

May 14, 2019

by Susan Van Dusen

Alan Tackett, Ph.D.

Alan Tackett, Ph.D.Professor of Biochemistry and Molecular Biology
   UAMS College of Medicine
Associate Director of Basic Research
   UAMS Winthrop P. Rockefeller Cancer Institute

Dr. Tackett’s research focuses on the identification of biomarkers and drug targets to treat melanoma. Specifically, he focuses on the identification of molecular and epigenetic pathways dysregulated in metastatic melanoma patients who are non-responsive to immune checkpoint therapy. Immune checkpoint therapy has revolutionized the treatment of metastatic melanoma, but only approximately half of patients show responsiveness to treatment. Dr. Tackett’s laboratory uses state-of-the-art proteomics and epigenomics to uncover the molecular differences between patient tumors that are either responsive or non-responsive to therapy. Targets and molecular pathways identified from these studies are biologically validated in melanoma cell culture and in vivo models.

Furthermore, Dr. Tackett is interested in how dysregulation of epigenetics, namely histone posttranslational modifications, reprograms certain melanomas to drive cancer progression and therapy responsiveness.

All of Dr. Tackett’s research is highly collaborative and translational as his team works closely with UAMS clinicians in the Department of Surgery, Division of Medical Oncology and Department of Pathology to obtain tissue samples for his studies. In addition to the ongoing cancer research in his laboratory, Dr. Tackett received funding from the National Institutes of Health in 2017 to create a Center of Biomedical Research Excellence (COBRE) focused on systems biology, which provides training for young scientists and core facility infrastructure development. In 2016, Dr. Tackett leveraged funding from the National Institutes of Health to develop a National Resource for Proteomics at UAMS, which provides a biomarker discovery platform to UAMS investigators as well as 23 other states and Puerto Rico.

Dr. Tackett’s Grants

NIGMS – 5 P20 GM121293-02

Center for Translational Pediatric Research

07/11/2017-06/30/2022

$1,618,994* (not all projects are cancer-related)

Role: PI

 

NIGMS – 5 R01 GM118760-03

Epigenetic Profiling and Enzymatic Regulation of H3K23ME3 During Cellular Differentiation

03/01/2017-01/31/2021

$37,500*

Role: PI

 

NIGMS – 5 P20 GM103429-18

Partnerships for Biomedical Research in Arkansas

Director of Research Technology Core

05/01/2015–04/30/2020

$193,619**

Role: PI

 

NCI – Awaiting NOA (Notice of Award) for specific project dates and budget figures.

Identification of Druggable Targets to Complement Melanoma Therapy

Role: PI

 

In addition to leading his own Centers of Biomedical Research Excellent (COBRE) grant (5 P20 GM121293-02), Dr. Tackett serves as a project mentor for two other UAMS COBRE grants: Center for Musculoskeletal Disease Research (PI: Charles O’Brien: 5 P20 GM125503-02) and Center for Studies of Host Response to Cancer Therapy (PI: Martin Hauer-Jensen: 5 P20 GM109005-05).

 

*cancer-related annual direct costs
**annual direct costs, not cancer-related, relevant to facilitation of campuswide research

Dr. Tackett’s Collaborators

Dr. Tackett has worked with dozens of researchers across numerous institutions and countries. Some of the collaborators for his most recent melanoma-focused studies include:

Juan Barreto, M.D., UAMS

Stephanie Byrum, Ph.D., UAMS

Rick Edmondson, Ph.D., UAMS

Laura Hutchins, M.D., UAMS

Sam Mackintosh, Ph.D., UAMS

Issam Makhoul, M.D., UAMS

Sara Shalin, M.D., Ph.D., UAMS

Sean Taverna, Ph.D., Johns Hopkins School of Medicine

Opportunities for Collaboration

I am always looking for opportunities to collaborate with colleagues at UAMS. I have an open-door policy for discussing new ideas, projects and collaborations. My scientific expertise is in systems biology technologies, which can often drive new collaborations.

You Might Not Know That …

I enjoy fishing, boating and spending time on the lakes in Hot Springs. That city has so much to offer and it is an easy drive from Little Rock. I may be biased because I was born there.

Cancer-Related Publications

1: Shields BD, Koss B, Taylor EM, Storey AJ, West KL, Byrum SD, Mackintosh SG, Edmondson R, Mahmoud F, Shalin SC, Tackett AJ. Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma. Cancer Res. 2019 Mar 15;79(6):1113-1123. doi: 10.1158/0008-5472.CAN-18-1722. Epub 2019 Jan 23. PubMed PMID: 30674537; PubMed Central PMCID: PMC6420873.

2: Mahmoud F, Shields B, Makhoul I, Avaritt N, Wong HK, Hutchins LF, Shalin S, Tackett AJ. Immune surveillance in melanoma: From immune attack to melanoma escape and even counterattack. Cancer Biol Ther. 2017 Jul 3;18(7):451-469. doi: 10.1080/15384047.2017.1323596. Epub 2017 May 17. Review. PubMed PMID: 28513269; PubMed Central PMCID: PMC5639850.

3: Shields BD, Mahmoud F, Taylor EM, Byrum SD, Sengupta D, Koss B, Baldini G, Ransom S, Cline K, Mackintosh SG, Edmondson RD, Shalin S, Tackett AJ. Indicators of responsiveness to immune checkpoint inhibitors. Sci Rep. 2017 Apr 11;7(1):807. doi: 10.1038/s41598-017-01000-2. PubMed PMID: 28400597; PubMed Central PMCID: PMC5429745.

4: Sengupta D, Tackett AJ. Proteomic Findings in Melanoma. J Proteomics Bioinform. 2016 Apr;9(4). pii: e29. Epub 2016 Apr 27. PubMed PMID: 27274624; PubMed Central PMCID: PMC4888906.

5: Mahmoud F, Shields B, Makhoul I, Hutchins LF, Shalin SC, Tackett AJ. Role of EZH2 histone methyltrasferase in melanoma progression and metastasis. Cancer Biol Ther. 2016 Jun 2;17(6):579-91. doi: 10.1080/15384047.2016.1167291. Epub 2016 Apr 22 Review. PubMed PMID: 27105109; PubMed Central PMCID: PMC4990393.

6: Sengupta D, Byrum SD, Avaritt NL, Davis L, Shields B, Mahmoud F, Reynolds M, Orr LM, Mackintosh SG, Shalin SC, Tackett AJ. Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma. Mol Cell Proteomics. 2016 Mar;15(3):765-75. doi: 10.1074/mcp.M115.053363. Epub 2015 Nov 30. PubMed PMID: 26621846; PubMed Central PMCID: PMC4813699.