The work in out laboratory is focused on the PI3K/Akt signaling pathway and cancer metabolism. My laboratory laid the groundwork to the role the serine/threonine kinase Akt as the major downstream effector of growth factor mediated cell survival (1997). My laboratory showed for the first time that Akt is sufficient and required for the activation of mTORC1 by growth factors (1998). Subsequently it was documented that Akt is the most frequently hyperactivated oncoprotein in human cancers. In 2001 we described for the first time the phenotype of Akt1^-/- mice and showed for the first time that genetic ablation of Akt sensitizes cells to cell death.

Over the years my laboratory has been delineating the mechanisms by which Akt affects tumorigenesis and metabolism, both at the cellular and organismal levels. At the organismal level my laboratory generated individuals and compound Akt isoforms KO mice and characterized their phenotypes and their susceptibility to cancer and diabetes. My laboratory showed for the first time that Akt1^-/- mice are resistant to cancer in mouse models (2006). Recently we have been employing systemic deletions of Akt isoforms and other genes after tumor onset to emulate drug therapy and to provide a genetic proof of concept for cancer therapy.

Other high impact discoveries include: 1) Showing that the ability of Akt to promote cell survival is dependent on the binding of mitochondrial hexokinase to mitochondria (2001). 2) Finding the Achilles’ heel of Akt to overcome cell survival and chemoresistance of cancer cells (2008). 3) Finding a new activity of AMPK as a regulator of NADPH homeostasis and the survival of cancer cells in response to energetic stress (2012). 4) Finding the mechanism by which Akt is required for adipogenesis (2012). 5)  Providing genetic proof of concept that hexokinase 2 could be a feasible target for cancer therapy (2013). 6) Showing that systemic deletion of Akt1 after tumor detection regresses tumors that are not driven by Akt activation (2015). 7) Showing that systemic deletion of both Akt1 and Akt2 in adult mice elicits rapid mortality, and that surprisingly hepatic deletion of Akt1 and Akt2 induces HCC with complete penetrance (2016). 8) Showing that hexokinase 2 (HK2) is required for HCC development and the combination of HK2 ablation and metformin or HK2 ablation and sorafenib markedly inhibits HCC (2018). 9) Systemic Akt1 deletion after tumor onset inhibits breast cancer metastasis in a non-cell autonomous manner by inhibiting pro-metastatic neutrophils (2020). 10)  Showing that HK2 has a novel catalytic independent activity as an AKAP that inhibits GSK3 to promote EMT and metastasis (2022). 11) Showing that HK2 is required for liver fibrosis and fibrotic gene expression via histone lactylation (2023). 12) The fatty acid transporter CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression (2023).

• 1978 M.Sc. degree received with highest distinction (summa cum laude)
• 1983 Prize of distinction from the Feinberg Graduate School, Weizmann Institute
• 1984-1986 Dr. Chaim Weizmann Fellowship
• 1986-1990 Weingart Foundation Fellowship
• 1990-1992 Alon Fellowship for new faculty, Israel (declined)
• 1990 Award of Louis Block Fund for Basic Research and Advanced Study
• 1990 Cancer Research Foundation Young Investigator Award
• 2009 University Scholar
• 2011- 2013 SPARK award (The Chicago Biomedical Consortium).
• 2013- present Distinguished University Professor
• 2019-2024 VA Research Career Scientist Award
• 2019 – Elected Fellow of the American Association for the Advances of Science (AAAs)
• AAAS Fellow (2019)
• UIC University Scholar (2009-2012)

NIH: R01CA090764
Hay (PI)
05/01/01-01/30/28
PI3K/PTEN/Akt Signaling and the Genesis of Cancer.

R01AG016927
Hay (PI)
08/01/98-01/31/24
The Role of Akt in Cell Survival and Cell Growth

R01CA258299
Hay (PI)
07/01/21-06/31/26
Hexokinase 2 and cancer therapy

Veteran Affairs:
I01BX005092
Hay (PI)
04/01/21-03/31/25
The role of AMPK and CD36 in breast cancer tumorigenesis and metastasis