Natalie Ahn

Natalie G. Ahn Ph.D. is a Professor of Chemistry and Biochemistry at the University of Colorado at Boulder. Her research is focused on understanding the mechanisms of cell signaling, especially in relation to phosphorylation and cancers.^[1] Ahn's work uses the tools of "classical chemistry" to work on understanding the genetic code and how genetics affects life processes.^[2] She has been a professor at University of Colorado at Boulder since 2003, where she is a Professor of Distinction.^[3] She was a Howard Hughes Medical Institute (HHMI) investigator between 1994 and 2014.^[4]

Biography

Past Education, Research, and Awards

Ahn earned her bachelor's degree from the University of Washington, Seattle in 1979, majoring in chemistry.^[5] In addition to enrollment in courses, Ahn conducted research in Lyle Jensen's lab, focusing on X-ray crystallography.^[5] This research helped with better understanding and visualizing the 3-D structure of proteins by using computational techniques with X-ray crystallography.^[6] Ahn also participated in undergraduate research in David Teller's lab, which studied Protein Hydrodynamics.^[5]

In 1985, she received her PhD in chemistry at the University of California, Berkeley.^[7] Here, Ahn worked with Judith Klinman, studying enzymology.^[5]

Ahn's first postdoctoral job was studying hormone receptor binding at the University of Washington with Christoph de Haen.^[5] Ahn then moved to Edwin Kreb's lab, where she started her career in signal transduction.^[5] In this lab, Ahn was "one of the first to describe MAP kinases and MAP kinase kinases." ^[5] Notable work from Ahn during this period of her life includes:^[4]

• "The MAP kinase cascade. Discovery of a new signal transduction pathways," in which Ahn used biochemical techniques used to highlight the cAMP kinase cascade, a specific protein kinase cascade.This new pathways is essential for signal transduction.^[8] This pathway is also prominent in cell growth and differentiation and is activated in nearly all cells.^[8] This pathway is more complex than a linear pathways due to regulation and feedback.^[8]
• "The mitogen-activated protein kinase activator," in which Ahn studied this activator (which is a growth factor and regulates the mitogen-activated protein kinase) through purification and characterization.^[9] Ahn was able to determine its primary structure and the protein kinase that regulates it activity.^[9]
• "Growth factor-stimulated phosphorylation cascades: activation of growth factor-stimulated MAP kinase," in which Ahn studied growth factors and their effect on protein phosphorylation, protein kinase activity, and protein serine/threonine phosphorylation.^[10] In this paper, Ahn also focused on microtubule-associated proteins (MAP), which are mediators of signaling and active a separate kinase.^[10]

She started working at CU-Boulder in 1992.^[11] Ahn was part of the Searle Scholars Program to fund young scientists' work in 1993.^[12]

Ahn was one of eight project collaborators who won a grant from the W.M. Keck Foundation for identifying proteins in a single cell type.^[13] In 2012, she was named College Professor of Distinction at the University of Colorado.^[11] In 2014, she became part of the Subcellular Pan-Omics for Advanced Rapid Threat Assessment (SPARTA) team which is a biochemical project supported by the Defense Advanced Research Projects Agency (DARPA).^[14] Ahn is published in BMC Bioinformatics,^[15] The EMBO Journal,^[16] the International Journal of Mass Spectrometry,^[17] Molecular and Cellular Biochemistry,^[18] and others.

Current Research and Work

Ahn is currently working at the University of Colorado focusing her research on cell signaling, information and proteomics, and molecular biophysics.^[3] Specific topics of her research include:

• Proteomics and Signal Transduction:
  • Ahn's lab's goal is to investigate new mechanisms that are responsible for regulation and cell signaling.^[3] In order to do this, Ahn uses mass spectrometry for protein profiling in combination with biochemical and cellular approaches to better understand a cell's response to signaling pathways. In addition, Ahn investigates the internal motions in protein kinases, specifically studying the coupling protein dynamics and catalytic function. Ahn studies the development of cancer by examining "signaling pathways that are activated in melanoma and influence cancer progression and cell behavior." ^[3]
  • Recent publications of this work include:
    • "Networks for the allosteric control of protein kinases," which focused on specific mechanisms on allosteric control and the role of protein kinases within a cell.^[19]
    • "Applying proteomics to signaling networks," which focus on information given by a genome sequencing and how this knowledge can apply to protein networks and cellular function.^[20]
• Wnt5A signaling:
  • Wnt5A is responsible for controlling embryonic body axis formation and can be found at high levels in melanomas, resulting in cell invasion. Ahn and her lab discovered the "Wnt5a receptor-actin-myosin-polarity (WRAMP) structure," which aids in directional cell movements by triggered membrane retraction. Ahn was able to determine WARMP structure using organelle proteomics.^[3]
  • Recent publications of this work include:
    • "Wnt5a control of cell polarity and direction movements by polarized redistribution of adhesion receptors," which focuses on the mechanisms of the Wnt pathways in melanoma cells.^[21]
    • "Wnt5a Directs Polarized Calcium Gradients by Recruiting Cortical Endoplasmic Reticulum to the Cell Trailing Edge," which specifies the formation, function, and structure of the WARMP structure.^[22]
• B-Raf signaling
  • In half of melanomas cells, B-Raf is a mutation and is responsible for cell transformation, invasion, and metastasis. In Ahn's lab, in order to profile phosphoproteins, she uses negative precursor ion mass spectrometry to discover and count phosphopeptides. Ahn has identified numerous different proteins with this method and with this information studied how cell mechanisms used in cancer therapy were affected by protein and protein signaling.^[3]
  • Recent publication of this work include
    • "Plexin B1 is repressed by oncogenic B-Rad signaling and functions as a tumor suppressor in melanoma cells," which focused on the B-Raf mutations in melanoma oncogenic melanomas cells, which in turn activated the B-Raf/MKK/ERK cascade.^[23]
    • "A Phosphoproteomic Comparison of B-RafV600E and MKK1/2 Inhibitors in Melanoma Cells," which studied the inhibitors of oncogenic B-RAF and MKK 1/2 and their response in B-RAP-positive melanoma patients.^[24]
• Proteomics Technologies:
  • In Ahn's lab, she uses multi dimensional LC-MS/MS in which complete mixtures of proteins are proteolyzed and peptides are then separated using liquid chromatography and the finally sequenced by MS/MS. This has allowed Ahn to identify over 8,000 proteins in each sequence of MS. Ahn's goal is to be more accurate and sensitive in these 2-D-LC-MS/MS techniques in assigning proteins.^[3]
  • Recent publications of this work include:
    • "Spectrum-to-spectrum searching use a proteome-wide spectral library," which focuses on the ambiguity of mass spectra to assign peptide sequences.^[25]
    • "Proteomics and genomics: perspective on drug and target discovery."^[26]
• Protein Kinase Dynamics:
  • In Ahn's lab, she uses hydrogen-exchange mass spectrometry (HX-MS) to discover and better understand protein motions on the inside of kinases, where energy fluctuations occur. Ahn's goal is to understand how the different protein dynamics are able to regulate catalytic activity in specific enzymes, most notably protein kinases. Ahn focuses on the MAP kinases called ERK2, which provides an ideal model due to its clear link between ERK2's activity and protein dynamics.^[3]
  • Recent publications of this work include:
    • Signal Transduction Pathways in Melanoma," which focuses on signaling between MMK/ERK and Rho GTASW. This has the ability to regulate melanoma progression.^[27]
    • "Networks for the allosteric control of protein kinases," which focuses on specific mechanisms of allosteric control and the role of protein kinases within a cell.^[19]

Current Leadership Position

Ahn was elected president of the American Society for Biochemistry and Molecular Biology (ASMBM) in the summer of 2015.^[5] She was previously a member of the council.^[5] She began attending the ASMBM meeting annually, while still a PhD student at the University of California, Berkeley.^[5] During one of these meetings, she gave her first public research talk.^[5] In addition, ASMBM provided financial aid for publication of one of Ahn's first accepted manuscripts, while she was a postdoc in Christoph de Haen's lab.^[5]

Works

• R.L. Khandelwal; J.H. Wang, eds. (6 December 2012). "The MAP kinase cascade". Reversible Protein Phosphorylation in Cell Regulation. Springer Science & Business Media. pp. 201–. ISBN 978-1-4615-2600-1. 
• Rony Seger, ed. (January 2004). "Methods in Functional Proteonomics". MAP Kinase Signaling Protocols. Springer Science & Business Media. pp. 263–. ISBN 978-1-59259-671-3. 
• J. E Celis, ed. (2006). "Protein Hydrogen Exchange Measured by Electrospray Ionisation Mass Spectrometry". Cell Biology: A Laboratory Handbook. Elsevier. pp. 443–. ISBN 978-0-12-164730-8. 

References

External links

• Her academic home page
• Her Howard Hughes Medical Institute bio