Mary D. (Molly) Frame
The focus of my research is in integrating signal transduction events with physical properties of blood flow at the microvascular level. Our long term research goals are to understand the two phase question of how solute distribution and transport are coupled in the microcirculation. We use both quantitative in vivo microcirculatory techniques in a hamster striated muscle model and in vitro cell culture techniques with macro- and microvascular endothelial cells to determine how vasoactive mechanisms are integrated to regulate blood flow distribution. In vivo, we examine mechanisms of nitric oxide mediated coordinated flow delivery to arteriolar networks. In vitro, we examine flow velocity profiles and endothelial cell responses to defined flow in a microchannel system which we construct at the Cornell Nanofabrication Facility, Cornell University.
Current Research Projects
- Project #1. Funded by The National Institutes of Health since 1996, this project examines physical and genomic mechanisms involved in the control of blood flow within the smallest blood vessels. The emerging picture is that flow is not controlled in individual vessels, but instead as a concerted effort by a specific group of vessels called a network. This involves multiple flow paths, and we examine resistance and flow in series and in parallel using computational fluid dynamics of low Re flow conditions. Of specific interest are the velocity profiles at bifurcation regions. The cellular mechanisms that appear to be most important in the living animal are wall shear stress sensing and vascular communication between adjacent cells through the gap junctions, including connexin 43. One particular type of response stimulated by nitric oxide initiates a reverberating communication along the network, with long lasting effects on subsequent responses. To further understand the role of physical and genomic mechanisms within the vascular network, we examine endothelial cell behavior within tissue engineered vascular networks in a scale model; we make this model at the Cornell Nanofabrication Facility.
- Project #2. Funded by the American Heart Association since 2000, this project examines how the connective tissue elements that hold small blood vessels in place also initiate vascular communication signals that regulate where the blood flow goes within a network. The hypothesis is that flow is coordinated at the level of the network to meet the metabolic needs of the tissue. Specifically, we examine the terminal arteriolar network control of flow by the vitronectin receptor. Important components to this response appear to be chloride channel activation and wall shear stress sensing and communication along the upstream flow path. By using a genomic approach developed in our lab, we alter the protein expression of individual proteins within the hamster cheek pouch tissue. We have determined a vital link between connexin 43 and flow sensing that is essential for the network to behave in concert.
- New projects expand the tissue engineering associated with Projects #1 and #2 with the goal of constructing vascular networks that are viable for implantation. Key in development of this project is use of nanofabricated biodegradable scaffolding made by our collaborators, Drs. Chu and Hsiao, in the Department of Chemistry, Stony Brook University.
- Ph.D. (Physiology), 1990, University of Missouri, Columbia
- 2002- Associate Professor, Department of Biomedical Engineering, Stony Brook University
Honors and Awards
- Graduate Student Society Annual Teaching Award. 2001
- Melvin L. Marcus Young Investigator Award, Finalist, American Heart Association. 1994
- Travel Award, 5th World Congress for Microcirculation. 1991
- NIH Post-doctoral Fellowship. 1990-1993
- NIH Pre-doctoral Fellowship. 1986-1989
- Curators Scholarship, University of Missouri, Columbia. 1976
Professional Activities and Affiliations
- Reviewer for:
- American Journal of Physiology
- Cancer Research
- FASEB Journal
- Journal of Vascular Research
- Microvascular Research
- Thrombosis Research
- Grants submitted to National Institutes of Health (1999-2002)
- Biophysical Society (1990)
- American Physiological Society (1990)
- American Heart Association, Circulation (1994)
- Biomedical Engineering Society (1999)
- American Association for the Advancement of Science (1990)
- Microcirculatory Society (1991)
- Program Committee, (1996-2000)
- Membership Committee, (2001-2005); Chair, (2002-2005)
- Registered Outside User of the Cornell Nanofabrication Facility (1994-2002)
- Mentor for Frontiers in Physiology, American Physiological Society (2000-2001)
- Mentor for National College Undergraduate Research (NCUR) (1998-2001)
- Mentor for Independent Research (undergraduates at Johns-Hopkins University, Keuka College, Holly College, University of Rochester) (1997-2002)
- Microcirculation Physiome Project (1998-2001)
- Biomedical Engineering Society Fall Meeting, Seattle, co-organizer of Circulation Track (2000)
- Isis Pharmaceuticals Co. (2000)
- Rensselaer Polytechnic Institute (Biomedical Engineering initiative, Whitaker Foundation) (2001)
- Bristol-Meyer Squibb (1994)
Educational Contributions and Experience
- Undergraduate students:
- Introduction to BME
- Honors Reading in BME
- Graduate students:
- Cellular signaling
- Human Physiology
- Topics in Vascular Biology
- Honors Readings in Microcirculation
- Medical Students:
- Physiology (cardiovascular, respiratory)
- Residents in Anesthesiology:
- ASA Content Outline
- Cadaver dissections
- Critical Reading Skills
- Senior Presentations for MARC
Selected Journal Articles
- MDS Frame, GB Chapman, Y Makino, IH Sarelius. Shear stress gradient over endothelial cells in a curved microchannel system. Biorheology, 35: 245-261, 1998.
- MDS Frame. Conducted signals within arteriolar networks initiated by bioactive amino acids. American Journal of Physiology: Heart and Circulation, 276: H1012-H1021, 1999.
- Mustafa SS, RJ Rivers, MDS Frame. Microcirculatory basis for non-uniform flow delivery with intravenous nitroprusside. Anesthesiology, 91(3): 723-731, 1999.
- Rivers RJ, and MDS Frame. Vascular communication initiated by increases in tissue adenosine. Journal of Vascular Research, 36: 193-200, 1999.
- MD Frame. Increased flow precedes remote arteriolar dilations for some micro-applied agonists. American Journal of Physiology: Heart and Circulation, 278: H1186-H1195, 2000.
- MD Frame and IH Sarelius. Flow disrupts F-actin central fibers in endothelial cells growing on a curved surface. Microcirculation, 7: 419-427, 2000.
- DN Noren, HJ Palmer, and MD Frame. Predicted wall shear rate gradients in T-type arteriolar bifurcations. Biorheology, 37: 325-340, 2000.
- RJ Rivers, JB Beckman, and MD Frame. Technique for using video-microscopy and indicator dilution for repeated measurements of cardiac output in small animals. Anesthesiology, 94: 489-495, 2001.
- MD Frame, JM Miano, J Yang, RJ Rivers. Localized adenovirus mediated gene transfer into vascular smooth muscle in the hamster cheek pouch. Microcirculation 8: 403-413, 2001.
- RJ Fox, and MD Frame. Regulation of flow and wall shear stress in arteriolar networks of the hamster cheek pouch. Journal of Applied Physiology, 92:2080-2088, 2002.
- MD Frame, R Fox, D Kim, A Mohan, BC Berk, C Yan. Diminished arteriolar responses in nitrate tolerance involve ROS and angiotensin II. American Journal of Physiology Heart and Circulation, 282: H2377-H2385, 2002.
- MD Frame. In vivo transfection in microcirculatory research. Current Contents, ISI, Philadelphia, in press 2002.
- Department of Surgery, University of Rochester, NY 2002
- Departments of Biomedical Engineering and Physiology/Biophysics, SUNY Stony Brook, NY 2002
- Department of Medical Biophysics, University of Western Ontario, Canada 2001
- Biomedical Engineering Department, Rensselaer Polytechnic Institute, Troy, NY 2001
- Isis Pharmaceuticals Co., Carlsbad, CA 2000
- Biomedical Engineering Program, Pennsylvania State University, University Park, PA 1999
- Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 1999
- Department of Pharmacology and Physiology, University of Rochester 1999
- Stanford Nanofabrication Facility, Stanford University 1998
- Department of Physiology and Biophysics, Louisiana State University, Shreveport 1995
- Department of Physiology and Mol. Med., Medical College of Ohio, Toledo 1995
- Department of Physiology, University of New Mexico, Albuquerque 1994
- Depts. of Emergency Medicine and Physiology, Louisiana State U., Shreveport 1993
- Cardiology Unit, University of Rochester Medical Center 1992
- Department of Physiology, University of Missouri, Columbia 1992
- Department of Biophysics, University of Rochester Medical Center 1989
- Department of Medical Physiology, Texas A&M University, College Station 1989
Recent Meetings (stop by and say Hi)
- A Sethi, LD Frame, S Malik, J Yang, MD Frame. Arteriolar network preconditioning response requires connexin 43 in hamster cheek pouch. Experimental Biology 2002, New Orleans, LA, April 19-24, 2002.
- MD Frame, RJ Fox, JJ Beckman. Chloride channel involvement in flow recruitment by vitronectin receptor stimulation. Experimental Biology 2002, New Orleans, LA, April 19-24, 2002.
- MD Frame, RJ Fox. Vitronectin receptor stimulation of remote vascular responses: role of connexin 43. Biomedical Engineering Annual Fall Meeting, Durham, NC, October, 2002.
- Z-G Jin, H Ueba, T Tanimoto, Ao Lungu, MD Frame, BC Berk. Src kinase-dependent transactivation of VEGF receptor Flk-1 is involved in fluid shear stress-induced eNOS activation and vasodilation. American Heart Association Scientific Sessions 2002, Chicago, IL, November 2002.