Welcome to the Flynn lab homepage

Our lab is funded by the National Institutes of Health to determine how the cellular signaling protein AFAP-110 can direct activation of oncogenic signals and regulate cytoskeletal integrity.  We have published over 50 original reports in this area of study and have been NIH funded continuously since 1993.  Our current area of focus is upon understanding how AFAP-110 can move to and activate cSrc, and subsequently, how podosomes or precursors to invadopodia form in response to this signal. 

Below is an image show AFAP-110 on stress filaments and its subsequent movement to podosomes that occurs upon Src activation (Flynn et al., 1993 MCB).

AFAP-110 is associated with stress filaments and cortical actin

Upon Src activation, AFAP-110 is localized to podosomes

AFAP-110 binds to the lateral sides of actin filaments as a nonamer and is an actin filament cross linking protein (Qian et al. 2004 J. cell. Biochem.):

The Pleckstrin Homology domain plays a key role in AFAP-110 function as a cSrc activating protein (Baisden et al., 2001 Oncogene):

AFAP-110 PH1 domain	BTK  PH domain
		(-) IP3
		(+) IP3

Loss of AFAP-110 from cells results in a deficit in cell adhesion, whereby cells adhere to fibronectin 2.7-fold less efficiently than wild type cells, over 40 minutes (Dorfleutner et al., 2007 J. Cell. Physiol.):

We can reduce AFAP expression in cells

We see reduced cell adhesion

cSrc activation is common in breast and ovarian cancer.  Transformation by activated cSrc results in major cell shape changes and can render cells resistant to chemotherapy.  It is possible that agents which block cSrc may promote sensitization to chemotherapy and affect a better outcome for patients.

PKCa and cSrc activation promote changes in adhesion, migration and invasion

A nanowire detector is in development to detect cancer biomarkers.  This is a collaborative effort with Dr.’s Nick Wu, Peter Gannett and William Petros.