Adrian Salic

  • Latest publications

    Jao C, Nedelcu D, Lopez L, Samarakoon T, Welti R and Salic A – 2015 Biooorthogonal probes for imaging sterols in cells, Chembiochem. in press.

    Signer RA, Magee JA, Salic A and Morrison SJ – 2014 Hematopoetic stem cells require a highly regulated protein synthesis rate, Nature 509(7498):49-54.

    Nedelcu D, Liu J, Xu Y, Jao C and Salic A – 2013 Oxysterol binding to the extracellular domain of Smoothened is required for vertebrate Hedgehog signaling, Nat Chem Biol, 9, 557-564.

    Tukachinsky H, Kuzmickas RP, Jao CY, Liu J and Salic A – 2012 Dispatched and Scube mediate the efficient secretion of the cholesterol-modified Hedgehog ligand, Cell Rep, 2(2), 308-20.

    Liu J, Xu Y, Stoleru D, and Salic A – 2012 Imaging protein synthesis in cells and tissues with an alkyne analog of puromycin, PNAS, 109(2), 413-8.

  • Prizes and Awards

    RR Bensley Award in Cell Biology, American Society of Anatomists, 2010

    Student Mentoring Award, BBS Program, Harvard Medical School, 2009

    American Asthma Foundation Early Excellence Award, 2009

    Armenise-Harvard Junior Faculty Grant, Department of Systems Biology: “The critical role of vertebrate Hedgehog lipid modification: a combined biochemistry and chemical biology approach”, 2007

    Sontag Foundation Young Investigator Award, 2007

    Beckman Young Investigator Award, 2007

    Rita Allen Foundation Scholar, 2006

    Smith Family Scholar in Biomedical Science, The Medical Foundation, 6006

Who he is

Adrian Salic received his PhD from Harvard University in 2000, working in the laboratory of Marc Kirschner. Adrian’s PhD thesis focused on the biochemistry of the Wnt signaling pathway, using frog embryos and extracts.

He then moved to the Department of Systems Biology at Harvard Medical School for a postdoctoral fellowship with Timothy Mitchison, where he studied mitotic chromosome segregation. Adrian was appointed Assistant Professor of Cell Biology at Harvard Medical School in 2005, and was promoted to Associate Professor in 2011. 

What he does

Communication between cells is critical for virtually every aspect in the life of a multicellular organism, beginning with the very earliest steps in embryonic development, all the way to its proper functioning as an adult. Defective cell-cell signaling, if it occurs during embryonic development, can led to birth defects, while if it happens in adults, can lead to diseases such as cancer. The Salic lab is interested in understanding the molecular mechanism by which animal cells send, receive and interpret signals.

To achieve this goal, the lab uses biochemistry, cell biology and chemical biology. Specifically, the lab focuses on two main directions: 1) Understanding the mechanisms involved in cell-cell signaling through a signaling pathway called the Hedgehog pathway; and 2) Synthesizing and validating novel chemical probes for microscopic imaging and functional assays of various biological molecules (including nucleic acids, proteins, lipids), in cells and in whole animals.

News from the Lab

Recent efforts in the lab were aimed at understanding two aspects of the involvement of cholesterol and cholesterol derivatives in the Hedgehog pathway. First, we focused on the unique cholesterol modification of the Hedgehog ligand, the protein that activates the pathway. This cholesterol modification makes the ligand very insoluble in aqueous media, such as the space between cells; yet the ligand is known to travel and signal to distant cells.

We discovered that cells produce a dedicated protein, which binds the Hedgehog ligand and shields its cholesterol moiety, thus greatly promoting its water solubility and thus its spread to faraway cells. Second, we investigated the role of oxysterols, a class of molecules derived from cholesterol by oxidation, which were known as strong activators of Hedgehog signaling. We determined that oxysterols activate the Hedgehog pathway by binding to a specific portion of a protein called Smoothened, which then activates Smoothened.

We also found that binding of oxysterols to Smoothened is important for Hedgehog signaling, and that one can devise novel inhibitors of Hedgehog signaling by finding drugs that block the interaction between oxysterols and Smoothened.