Alessia Fornoni, MD, PhD

Assistant Professor of Clinical Medicine

tel: 305-243-6251
fax: 305-243-4404
pager: 305-750-1592

Education

Universita' degli Studi di Pavia Pavia, Italy	Ph.D.	Molecular Pharmacology	2000
Universita' degli Studi di Pavia Pavia, Italy	M.D.	Nephrology	1995

Dr Fornoni obtained her MD and her PhD degree in Medical Pharmacology at the Universita' degli Studi di Pavia (Italy). She later joined the laboratory of Renal Cell Biology (Vascular Biology Institute) at the University of Miami, where she worked on animal models of diabetic nephropathy and on the role of mesangial stem cells progenitors under the direct supervision of Drs Liliane and Gary Striker. After her post-doctoral fellowship, Dr Fornoni completed the Internal Medicine and Nephrology training at the University of Miami (Basic Scientist Investigator pathway). She is Board Certified in both Internal Medicine and Nephrology. She currently devotes 75% of her time to research and 25% to patient care. Dr Fornoni research interest is focus on diabetes, with particular interest in diabetic nephropathy and pancreatic islets function in both type 1 and type 2 diabetes. Dr Fornoni research resulted in the finding that glucose may irreversibly affect the phenotype of glomerular mesangial cells, mainly through direct alteration of unstable regions of genomic DNA. Dr Fornoni is currently interested in the intracellular signaling pathways activated in islets and podocytes by inflammation. Dr. Fornoni research goal is to translate her basic science findings into clinical research through the identification of new therapeutic targets for the improvement of diabetes and its complications.

Clinical Specialties

Diabetic nephropathy, glomerular diseases, inherited nephropathies, chronic kidney disease

Research Interests

Dr Fornoni is currently interested in the intracellular signaling pathways activated in islets and podocytes by inflammation. Dr. Fornoni research goal is to translate her basic science findings into clinical research through the identification of new therapeutic targets for the improvement of diabetes and its complications.

Publications

List of publications by Alessia Fornoni, MD, PhD

Fornoni, A., O. Lenz, I.Tack, M. Potier, S.J. Elliot, L.J. Striker and G.E. Striker, Matrix Accumulation in Mesangial Cells Exposed to Cyclosporine A Requires a Permissive Genetic Background, Transplantation, 70:587-593, 2000

Esposito, C., A. Fornoni, F. Cornacchia, N. Bellotti, G. Fasoli, A. Foschi, I. Mazzucchelli, T. Mazzullo, L. Semeraro and A. Dal Canton, Cyclosporine Induces Different Responses in Human Epithelial, Endothelial and Fibroblast Cell Cultures, Kidney Inter

Cornacchia, F., A. Fornoni, A.R. Plati, A. Thomas, Y. Wang, L. Inverardi, L.J. Striker and G.E. Striker, Glomerulosclerosis is Transmitted by Bone-Marrow Derived Mesangial Cell Progenitor. Journal of Clinical Investigation, 108:1649-56, 2001

Fornoni, A., F. Cornacchia, G.A. Howard, B.A. Roos, G.E. Striker and L.J. Striker, Cyclosporin A Affects Extracellular Matrix Synthesis and Degradation by Mouse MC3T3-E1 Osteoblasts In vitro, Nephrology Dialysis Transplantation, 16: 500-505, 2001

Fornoni, A., H. Li, A. Foschi, G.E. Striker and L.J. Striker, Hepatocyte Growth Factor, but not Insulin-like Growth Factor I, Protects Podocytes Against Cyclosporin A-Induced Apoptosis, American Journal of Pathology, 158:275-280, 2001

Zheng, F, A. Fornoni, S.J. Elliot, Y. Guan, M.D. Breyer, L.J. Striker and G.E. Striker, Upregulation of Type I Collagen by TGF-beta in Mesangial Cells is Blocked by PPAR-gamma Activation, American Journal of Physiology Renal Physiology, 282:F639-F648,

Fornoni, A, L.J. Striker, F. Zheng and G.E. Striker, Reversibility of Glucose-Induced Changes in Mesangial Cell Extracellular Matrix Depends on the Genetic Background, Diabetes, 51:499-505, 2002

Fornoni, A., Y. Wang, O. Lenz, L.J. Striker and G.E. Striker, Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice, Journal of the American Society of Nephrology, 1

Fornoni, A., O. Lenz, L.J. Striker and G.E. Striker, Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-prone Mice, Diabetes, 52:2594-2602, 2003

Vazquez-Padron, R.I., D. Lasko, S. Li, L. Louis, I.A. Pestana, M. Pang, C. Liotta, A. Fornoni, A. Aitouche and S.M. Pham, Aging Exacerbates Neointimal Formation, and Increases Proliferation and Reduces Susceptibility to Apoptosis of Vascular Smooth Mus

Zheng, F., F. Cornacchia, I. Schulman, A. Banerjee, Q.L. Cheng, M. Potier, A.R. Plati, M. Berho, S.J. Elliot, J. Li, A. Fornoni, Y.J. Zang, A. Zisman, L.J. Striker and G.E. Striker, Development of Albuminuria and Glomerular Lesions in Normoglycemic B6

Lenz, O., Fornoni, A. and Contreras G. Defining the Role of Mycophenolate Mofetil in the Treatment of Proliferative Lupus Nephritis. Drugs 65:1-9, 2005

Fornoni, A. and L. Raij, Metabolic Syndrome and Endothelial Dysfunction, Current Hypertension Reports, Current Hypertension Reports, 7:88-95, 2005

Karl, M., M. Potier, I.H. Schulman, A. Rivera, H. Werner, A. Fornoni and S.J. Elliot, Autocrine Activation of the Local Insulin-Like Growth Factor I System Is Up-Regulated by Estrogen Receptor (ER)-Independent Estrogen Actions and Accounts for Decrease

Contreras G, Lenz O, Pardo V, Borja E, Cely C, Iqbal K, Nahar N, de La Cuesta C, Hurtado A, Fornoni A, Beltran-Garcia L, Asif A, Young L, Diego J, Zachariah M, Smith-Norwood B. Outcome in African American and Hispanics with lupus nephritis. Kidney Inte

Fornoni A, Rosenzweig SA, Lenz O, Rivera A, Striker GE, Elliot SJ. Low IGFBP-2 expression is responsible for increased IRS-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis. Endocrinology, 2006 Jul;147(7):3547-54.

Lenz O, Fornoni A, Contreras G. New directions in the management of severe lupus nephritis. Minerva Urol Nefrol, 58:29, 2006.

De Freitas O, Lenz O, Fornoni A, Materson BJ. The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure. Vascular Health and Risk Management, 2: 139-144, 2006.

Awards & Recognition

• Professional development seminar award
  American Society of Nephrology
• Amgen junior faculty award
  
• Stanley Glaser Award
  Institutional support for promising young scientists

Personal Statement

My overall goal has always been to pursue a career in Academic Medicine as physician-scientist, where the interaction between clinical and basic science is the strongest, and the daily teaching and learning experience essential to promote new discoveries in science. To achieve this, I planned since the very beginning of my medical school (1989) a long training program.
I obtained my MD degree from the University of Pavia, Italy, in 1995. Since a PhD degree was also a requirement to obtain an academic position, I enrolled in a PhD program in Medical Pharmacology at the University of Pavia. At that time, the University of Pavia was in the process of developing a kidney transplant program, and I decided to focus my research on the molecular mechanism of renal toxicity of calcineurin inhibitors. In the third year of my PhD program, in order to complete some of the essential experiments required to complete my PhD thesis, I came to the United States in the laboratory of Drs. Lillian and Gary Striker at the University of Miami Miller School of Medicine. In fact, it is under the direct supervision of Gary and Lilinae Striker that I learned most of the cellular and molecular biology expertises I have accumulate to date. In particular, I learned how to obtain primary culture of any type of glomerular cells and of vascular smooth muscle cells from any vascular bed. While completing my PhD in the laboratory, I had the opportunity to round with the clinical team at Jackson Memorial Hospital, where it became immediately clear that diabetes and its complications represented a major health care burden. I soon realize how difficult it is for a diabetic patient to cope with a disease that is highly demanding in terms of life style changes and that is often progressing to major complications affecting the quality of life and is associated with very high cardiovascular mortality. Since one of the major focus of the laboratory of Dr Liliane and Gary Striker has been on the mechanism of diabetic nephropathy and on the role of genetic background in the development of this complication, I requested to prolong my training in this laboraotory with a Post Doctoral fellowship in the field of diabetic nephropathy. During this period (2000-2002), I have been particularly interested in the isolation and characterization of glomerular cells from different models of diabetes. I discovered that those cells retain their diabetic phenotype in vitro, even when they are subtracted from a diabetic enviroment. Thus, in order to investigate the nature of this stable phenotypic change, I investigate whether diabetes can alter genomic DNA, and I found that chronic exposure to hyperglycemia can modify the length of microsatellite repeat regions in the promoter of genes that are relevant to the development of diabetic nephropathy, such as matrix metalloproteinase (MMP)-9. Interestingly, this genetic modification in the promoter of key genes is responsible for a stable change in gene expression and occurs only in those mice that are susceptible to the development of complications. My work resulted in several publications in peer-reviewed journals and presentations at national and international meetings. In particular, during my post-doctoral fellowship, I published 6 manuscripts as first author and I contributed to several works from others. Most importantly, my post-doctoral experience resulted in the development of a strong passion and full commitment to a career in Academic Medicine devoted to the investigation of mechanisms of disease in diabetes. Since my real dream was to become a physician-scientist, I temporarily left the laboratory to complete my medical training. I became board-certified in Internal Medicine in 2004 and in Nephrology in 2005. In the course of my clinical training, I was mainly exposed to a population of patients with chronic kidney disease and end stage renal disease requiring renal replacement therapy. In fact, being diabetes the most common cause of ESRD in the United States, I interact on a daily basis with a large population of patients with either type 1 or type 2 diabetes. However, during my clinical training, it has been very frustrating to realize that for many patients, a very strict control of modifiable risk factors such as glycemia and blood pressure are necessary but not sufficient to prevent the development of severe complications. This clinical observation shifted my research interest to the cure of diabetes rather than solely to the cure of diabetic complications. Thus, after I accepted a position as Assistant Professor in Clinical Medicine at the University of Miami, Division of Nephrology and Hypertension, I requested to join the Diabetes Research Institute shortly thereafter, where I was offered independent office and laboratory space for my research. In fact, since the Diabetes Research Institute mission is to cure diabetes, I believe it represents the best setting for the development of a young physician-scientist as I am. In fact, the Diabetes Research Institute has offered me the possibility to interact on a daily basis with principal investigators that are focus on different areas of diabetes research, including islet physiology and function, islet transplantation and cytoprotection, pancreas development, autoimmunity and immunotolerance. Dr Camillo Ricordi, the scientific director of the institution, has identified Dr Luca Inverardi as my direct mentor, given his long-term interest in islets cytoprotection. The collaboration with Dr Ricardo Pastori and Dr Antonello Pileggi, with their respective expertise in molecular biology and animal model of islet transplantation, will be essential for the success of the proposed research. In addition, the interaction with the group directed by Dr Per-Olof Berggren is essential to characterize how islet physiology can be affected by inflammatory pathways.
Dr. David Roth, Chief of the Division of Nephrology and Hypertension, has granted me 75% protected time for research. This will allow me to develop an independent career in academic and laboratory research while maintaing a clinical focus and thus fulfilling my goal of becoming a physician-scientist. My research interest is currently focused on the role of inflammation in diabetes; I am developing independent projects that investigate how inflammation can affect the function of human islets and be responsible for the initiation of diabetic complications. In the past 10 months, I have been able to obtain several small awards which represent the seed funds of my research program: 1) Juvenile Diabetes Research Foundation, principal investigator of a pilot project as part of a Center Grant, 2) Stanley Glaser Award, for research in intracellular signaling on human islets and 3) Amgen Junior Faculty Award, focusing on the role of inflammation as an early biomarker and initiator of damage in diabetic nephropathy. With the above support, I generated data allowing the preparation of a first manuscript and serving as the basis for future grant applications. The JDRF pilot project is partially related to the proposed application, since it investigates through mice knock out models the specific role of sub-classes of intracellular kinases activated by inflammation in islet function and viability. The Stanly Glaser award also allows me to gain familiarity with the use of protein transduction technology to target intracellular kinases activated by inflammations. Finally, the Amgen award will allow me to understand how the chronic inflammatory environment that characterize diabetes can influence the development of diabetic nephropathy. My goal is to discover new targets for the therapy of diabetes and its complication. I have established collaborations with clinical scientist involved in multi-center clinical trials in the field of diabetes and chronic kidney disease as well as with pharmaceutical companies developing new anti-inflammatory medications for other applications. In particular, I collaborate with the investigators of the African American Study of Kidney Disease and Hypertension (AASK trial) to identify the role of inflammation in the progression of chronic kidney disease. In addition, I established a collaboration with Celgene Corporation (Dr Brydon Bennett) to test the role of a new potent anti-inflammatory compound which has the ability to improve insulin signaling. In fact, the use of this compound is the subject of the proposed research. I believe this set-up will allow for a rapid translation of my bench findings to patients care. If the proposed research will lead to the identification of a new drug able to improve both pancreatic islets viability and function, both patients in need of islet transplantation and/or insulin treatment may benefit from this medications. Finally, I truly believe that as long as my enthusiasm and passion for research prevail, along with compassion for the patients I care for, my efforts will result in a successful academic career in the field of diabetes.