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Sacks' Laboratory

Welcome to the website of the Sacks' laboratory! Our research focuses primarily on intracellular signal transduction regulated by scaffold proteins and Ca2+-sensing proteins. Current projects seek to identify new binding partners to those proteins, and to explore functional implications in cellular functions, physiology, and pathology. The research integrates an array of cell biology, biochemistry, and molecular biology techniques.

Our laboratory is part of the National Institutes of Health intramural research program. We are located in the Clinical Center on the NIH main campus in Bethesda, Maryland.

The research in the laboratory is directed towards elucidating the role of calmodulin and IQGAPs in signal transduction pathways.

Our major areas of interest include the disruption of the normal signaling pathways that result in cancer and microbial pathogenesis.

A diverse array of biochemical, cell biological, and molecular biological approaches are used in these investigations.

Research areas include:

Dr. David B. Sacks

Senior Investigator
National Institutes of Health
Email: sacksdb@mail.nih.gov
Phone: 301-496-3386

Read Curriculum Vitae

Selected Bibliography:

  • Thines L, Shi S, Sayedyahossein S, Li Z, Roushar FJ, Thomas R. Kleyman TR, Sacks DB. The scaffold protein IQGAP1 regulates the epithelial Na+ channel. J Biol Chem. 2025 Nov 7:110919. doi: 10.1016/j.jbc.2025.110919. Epub ahead of print. PMID: 41207626.
  • Sayedyahossein S, Huang K, Zhang C, Karimi M, Bahmani M, O'Donnell BL, Wakefield B, Li Z, Johnston D, Leighton SE, Huver MS, Dagnino L, Sacks DB, Penuela S. Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma. FEBS J. 2025; 292:1633-1653. doi: 10.1111/febs.17396. PMID: 39786847.
  • Sayedyahossein S, Sait MRB, Li Z, Banerjee R, Tran A, Thines L, Karimi M, Bahmani M, Mishan N, Borzou P, Hassan SA, Sacks DB. KSR is a scaffold for the Hippo pathway. Commun Biol. 2025; 8, 1725. https://doi.org/10.1038/s42003-025-09009-4.
  • Thines L, Jang H, Li Z, Maloney R, Sayedyahossein S, Nussinov R, Sacks DB.  Disruption of Ca2+/calmodulin:KSR interaction lowers ERK activation. Protein Science 2024;33(5): e4982. https://doi.org/10.1002/pro.4982
  • Martín-Vega A, Ruiz-Peinado L, García-Gómez R, Herrero A, de la Fuente-Vivas D, Parvathaneni S, Caloto R, Morante M, von Kriegsheim A, Bustelo XR, Sacks DB, Casar B, Crespo P. Scaffold coupling: ERK activation by trans-phosphorylation across different scaffold protein species. Science Advances 2023 Feb 15;9(7):eadd7969. doi: 10.1126/sciadv.add7969. Epub 2023 Feb 15. PMID: 36791195; PMCID: PMC9931222.
  • Thines L, Li Z, Sacks DB.  IQGAP1 is a phosphotyrosine-regulated scaffold for SH2-containing proteins. Cells 2023; 12(3):483; https://doi.org/10.3390/cells12030483.
  • Thines L, Gorisse L, Li Z, Sayedyahossein S, Sacks DB.  Calmodulin activates the Hippo signaling pathway by promoting LATS1 kinase-mediated inhibitory phosphorylation of the transcriptional coactivator YAP. J Biol Chem. 2022 May;298(5):101839. doi: 10.1016/j.jbc.2022.101839.
  • Sayedyahossein S, Smith J, Barnaeva E, Li Z, Choe J, Ronzetti M, Dextras C, Hu X, Marugan J, Southall N, Baljinnyam B, Thines L, Tran AD, Ferrer M, Sacks DB. Discovery of small molecule inhibitors that effectively disrupt IQGAP1-Cdc42 interaction in breast cancer cells. Scientific Reports 2022; 12:17372. https://doi.org/10.1038/s41598-022-21342-w
  • Ramshekar A, Wang H, Kunz E, Pappas C, Hageman GS, Chaquor B, Sacks DB, Hartnett ME. Active Rap1-mediated inhibition of choroidal neovascularization requires interactions with IQGAP1 in choroidal endothelial cells. FASEB J 2021;35(7):e21642. doi.org/10.1096/fj.202100112R.
  • Parvathaneni S, Li Z, Sacks DB. Calmodulin influences MAPK signaling by binding KSR1. J Biol Chem 2021; 296: 100577. doi: 10.1016/j.jbc.2021.100577.
  • Sayedyahossein S, Huang K, Li Z, Zhang C, Kozlov AM, Johnston D, Nouri-Neja D, Dagnino L, Betts DH, Sacks DB, Penuela S. Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism. J Biol Chem 2021; 296: 100478. doi: 10.1016/j.jbc.2021.100478.
  • Hedman AC, Li Z, Gorissse L, Parvathaneni S, Morgan CJ, Sacks DB. IQGAP1 binds AMPK and is required for maximum AMPK activation. J Biol Chem 2021; 296: 100075. doi: 10.1074/jbc.RA120.016193.
  • Zhang M, Jang H, Li Z, Sacks DB, Nussinov R. B-Raf autoinhibition in the presence and absence of 14-3-3. Structure 2021; 29:768-777.
  • Quinn NP, Garcia-Gutierrez L, Doherty C, von Kriegsheim A, Fallahi E, Sacks DB, Matallanas D. IQGAP1 is a scaffold of the core proteins of the Hippo pathway and negatively regulates the pro-apoptotic signal mediated by this pathway. Cells 2021; 10, 478. https://doi.org/10.3390/ cells10020478