DR. RICHARD A. GATTI
PERSPECTIVES AND GOALS

Over the years, I have tried to show students that learning is fun, that a dedicated professor works as hard as a struggling student, that studying and learning never end, and that you have to enjoy learning in order to teach. I have been rewarded by gaining the genuine friendship of many students. While trying to encourage those with the right attitudes and qualities, to maximize their chances of early fulfillment and recognition, I have also taken chances on students who I believed were slow starters or distracted by a disadvantaged environment. Only a handful of students have disappointed me. Of course, I do not know how many other students I have simply discouraged by this same philosophy!

I have participated in teaching a variety of courses at the university over the past twenty years. These include: Mapping the Human Genome (Path255), Medical Genetics, Genetics Training Program (Genet 201), and General Pathology (M201). I developed Path255 nine years ago for medical students but it is now taken primarily by graduate students from a variety of departments. It is taught each Spring Quarter,with Dr. Wayne Grody. Each session is divided into a) a didactic overview of a unifying genetic concept (presented by either Gatti or Grody), 2) a student presentation, which is selected from a predetermined list of important mapping techniques, and 3) a review by Dr. Gatti of various updated genetic maps (i.e., mapped polymorphic markers, genes, recombination fractions, homologous species). The student evaluations are uniformly laudatory. Course preparation takes approximately 8 hours per week in the Spring Quarter. I also taught Immunopathology M258D, organized by Dr. David Porter, for ten years.

Last Winter Quarter (98-99), I began teaching a new graduate course, Ataxia-Telangiectasia, as part of the Molecular Mechanisms of Disease (Path 298B). I taught this course with Ram Iyer, PhD. He organized an extensive workbook of seminal discoveries in the A-T field. Since the gene for this disease impacts upon many biological systems (e.g. immunology, radiation biology, neural development, cancer risk, cell cycle control, and cell signalling) we thought it would be an ideal model for bridging medicine and biology. Each week, two students were asked to review a recommended paper, and any relevant literature. Discussion was lively. Student evaluations were good. We intend to teach this course every other year.

In the alternate years (under the same Molecular Mechanisms of Disease (Path 298B)), Dr. Iyer and I teach another course, DNA Repair and Cancer Risk, which we hope will alert the students of the growing relationship between cancer and genome instability. This should provide many new ideas for research projects for graduate work since almost all the genes for the cancer-prone disorders we have selected have been cloned. We provide a 3-volume workbook of key papers and reviews.

I am on the department's Graduate Training Committee and have played an active role in graduate student recruitment through the school-wide ACCESS program. With Dr. Wayne Grody, I participate in weekly one-hour diagnostic molecular pathology teaching conferences for housestaff and graduate students interested in biotechnology. I deliver approximately one invited seminar each month: 1) to other departments in the Schools of Medicine or Life Sciences, 2) to other hospitals (West Hills, St. Joseph's Orange County, Kaiser Permanente-Sunset, St. Joseph's Burbank, Hinterlands Pediatric Society) and institutes, and 3) to scientific conferences in the fields of genetics, immunology, neurology, pathology, pediatrics, radiobiology, and cell biology. I am on the teaching faculty of the UCLA Intercampus Medical Genetics Training Program, the Biomathematics Training Program, the Mental Retardation Research Center's training program (www.mrrc.npi.ucla.edu), the Medical Genetics Training Program, and the NIH MARC visiting lecturer program for providing faculty assistance to academic programs focusing on the education of underpriviledged students.

 

 

I. Graduate students trained

Daniel Weeks-- PhD Biomath/Genetics UCLA 12/89; Post-doc Columbia Univ 12/89--92; Assist Prof Univ Pittsburgh 92-94; Assoc Prof at Oxford 12/94--97; Prof Univ Pittsburgh 98--

Patrick Charmley-- PhD Immunology UCLA 1/90; Post-doc at Cal Tech 1/90-8/91; Assoc Res at DARWIN, Seattle 3/95--

Tatiana Foroud -- PhD Medical Genetics Univ Indiana 4/90
Certified Medical Geneticist, Indiana 97--

Wei Shan -- MS. Molecular Biology UCLA 6/89 Post-doc at Virginia Mason 8/91--

Julie Nyugen -- MS. Biology Long Beach State 6/92 Grad stud Exp Path UCLA 6/94--

Sharon Teraoka -- PhD. Molecular Biology UCLA 8/92 Post-doc at Virginia Mason 9/92--Member, Virginia Mason Res , Seattle 9/97--

Leslie Knapp -- PhD candidate Anthropology UCLA 3/91--??

Vickie Cortessis-- PhD Publ Health UCLA 7/93 Assist Prof UCLA USC 00--

Ethan Lange -- Grad stud Appl Math UCLA 9/91 and U. Michigan 96--

Teresa Liang -- Ph D candidate Exp Path UCLA 9/91/97 Post-doc UCLA JSEI 97--

Esra Iscen -- graduate student UCLA 1991. PhD Biology Bogazici Univ 6/92. Assist Prof Bogazici Univ 97--

Milhan Telatar-- PhD Mol Biology Bogazici Univ 6/94 Post-doc at UCLA 6/94 -98
Assist Res UCLA 12/98 --

Nancy Uhrhammer-- PhD. Exp Path UCLA 4/95 Post-doc at Yale Univ 4/95-7/97
Assis Member Jean Perrin Cancer Center,France 7/97-

Eric Sobel -- PhD Biomath/Genetics UCLA 9/95 Post-doc at Univ Mich 9/95-97
Post-doc at Stanford 97-99 Assist Prof at UCLA 11/99--

Sara Becker-- Grad student Exp Path UCLA 6/95--

Helen Chun -- Graduate student Exp Path UCLA 7/95--

Chih-Hung Lai -- Graduate student Exp Path UCLA 7/98--

Daniel Menendez Grad student U Mexico 4/98-6/98

Sepideh Shiekavandi MS candidate Cal State Northridge 7/96--

Mary Ho MS Chemistry UCLA 97-99 UC Berkeley Law School 99--

 

II. Post-doctoral training

Sujata Chiplunkar, PhD. Microbiol Univ Baroda 91 Post-doc Path UCLA 9/91--6/94
Post-doc Cedars-Sinai Hosp 6/94-97 Post-doc UCLA JSEI 97-99

Huanming Yang, PhD Mol Biol Copenhagen Univ 88 Post-doc Harvard Univ 88-92 Post-doc Path UCLA 92--93 Assoc Prof Beijing Union Med 93-97 Prof Beijing Union Med 97--

Xiaoguang Chen, PhD Hunan Medical Univ 90. Post-doc Path UCLA 92-94. Post-doc at Cedars-Sinai 94-98. Resident in Medicine, Baylor 98--

Nitin Udar, PhD Microbiol Univ of Baroda 91 Post-doc Path UCLA 92-96. Res Assoc UCLA JSEI 96-

Lan Yang, MD Hunan Medical Univ 90 Post-doc Path UCLA 93-94 Post-doc USC 94--

Shunbin Xu, MD Beijing Univ Med School 1991 Post-doc Beijing Med Union 91-93
Post-doc Path UCLA 93-95 Grad stud Johns Hopkins Univ 95-00

Olivier Bay, MD Univ Besancon Med Sch 92. Post-doc Path UCLA 94-97.
Assoc Member,Jean Perrin Cancer Center,France 97--

Zhijun Wang, MD Xian Univ Med 92. Post-doc Path UCLA 93-97. Resident in Pediatrics, CHOC 97--

Lai-Qian Tai, MS Xian Univ Pharmacology 93. Post-doc Path UCLA 94--97. Lab supervisor, CHOC 97--

Jason Hou, PhD Univ Houston 94. Post-doc Path UCLA 94--95

Midori Mitsui, PhD Biochemistry Univ Paraguay 94. Post-doc Path UCLA 98--

Mahnoush Babaei, MD Univ Tehran, 97. Post-doc Path UCLA 98--

Neghar Khanlou, MD Univ Paris 1995 Post-doc Path UCLA 98 --

 

 

III. Undergraduate students (1995-1999)

Arash Naeim, 91, 92, 94. MD UCLA 97. Resident in Oncology, UCLA 99--

Jeff Polakow 94-96 BS Harvey Mudd. 97 Grad school in Artificial Intelligence (?)

Armand Dorian, 93-95. MD U. Hawaii 98. Resident in Medicine, UCLA 99--

Jay Wilson 98-99. UCLA graduate ACCESS 99--

Jeff Suh 98-99. Medical student UCLA 99--

Richard Cheng 97--

Carolyn Clark 99--

Kristin Martinez 99--


IV. Visiting Professors

Ozden Sanal,MD. 87-89. Professor of Pediatrics Hacettepe Univ Ankara, Turkey 91--

Asli Tolun,PhD. Molecular Biology. 89,90,91. Professor Bogazici Univ Istanbul,Turkey

Gwyn Bebb,MD. 96. Assistant Professor University of British Columbia, Vancouver, Canada

Minna Nystrom,MD,PhD. 96. Univ Helsinki,Biochemistry,Helsinki, Finland

Shiela Ungers,MD. 96-97. Assistant Professor Hospital for Sick Children, Toronto, Canada. Post-doc UCLA/CSMC Genetics Training Program 98--

Sara Frias,PhD; 97. National Childrens Hospital, Mexico City, Mexico

Emilio Roya,PhD; 98. Univ Mexico, Mexico City, Mexico

 

 

RESEARCH

For the past twenty years, I have been trying to develop a therapeutic approach for a progressive and fatal disorder of childhood called ataxia-telangiectasia (A-T). In 1988, using a large Amish pedigree from Pennsylvania, we localized the gene to chromosome 11q22-23. In 1995, the gene (ATM) was isolated by positional cloning, due to the efforts of an international consortium organized by the PI. Since then, the A-T research community has grown in many directions and the biology of the ATM gene has become more interesting and complex. Within the past year, relevant papers have appeared in Cell, Nature, Science, Nature Medicine, Nature Genetics, and Amer J Hum Genetics... I have been a coauthor on many of these. It appears that the ATM gene activates (phosphorylates) p53, the "guardian of the genome"; it also activates more than ten other substrates that control cell cycle checkpoints and intracellular signalling. This somehow leads to cancer in one-third of A-T patients.

My lab presently includes a senior research associate, 3 post-docs, 3 graduate students, 2 technicians, and 3 undergraduates. We are the leading lab worldwide for diagnosing A-T and NBS1, and we have defined more than half of the known ATM mutations. We are collaborating on the role of ATM in embryonic development with Harley Kornblum (UCLA, Pharmacology). We are exploring the possibility of neural stem cell engraftment with John DeVellis (UCLA, MRRC). In collaboration with David Rawlings (UCLA, Pediatrics), we are attempting to purify ATM to determine the protein's structure by cryoEM, in collaboration with Phoebe Stewart (UCLA, Pharmacology).

The laboratory is developing a set of genetic typing reagents called Molecular Beacons, in collaboration with Sanjay Tyagi and Fred Kramer (PHRI,NYU). We continue to identify new ATM mutations in new populations, including Hispanic-American, Spain, Mexico, Brazil, Argentina, Chile, Equador, Bolivia, as well as Turkey, and Iran. The lab continues to work closely with Patrick Concannon (Virginia Mason Research Center, Seattle) on curating the ATM Mutation Database website (http://www.vmresearch.org/atm.htm) and in the identification of new human disorders assoicataed with radiosensitivity. In collaboration with Nitin Udar (UCLA, JSEI) we are cloning and sequencing the pufferfish ATM ortholog gene so that amino acid conservation can be compared when evaluating potential human mutations. In an attempt to create new reagents with which to analyze the intracellular role of ATM, Ram Iyer (UCLA,Pathology) is developing ATM-related ribozymes that are then being utilized in our laboratory. Each of these collaborations allows the students to interact with other laboratories and investigators, so that they can learn to collaborate in analyzing complex biological and medical problems.

Each week I meet with indiviual laboratory members for one hour to review experimental data and plan new experiments. On Monday mornings, we have a general lab meeting to hear progress reports (organized by a different lab member each week); this is also a time for joint tactical discussions. In addition, one lab member presents either a work-in-progress seminar or a review of a publication that is pertinent to A-T research.

I have organized five of the eight international workshops on ataxia-telangiectasia: ATW2 (Immunol Today 5: 121, 1984), ATW3 (Canc Res 47: 4750, 1987), ATW4 (Canc Res 49:6162, 1989), ATW5 (Canc Res 53, 438, 1993) and ATW8 (Canc Res 59:3845,1999). Reports resulting from the second and fifth meetings were published as books (Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood Eds RA Gatti, M Swift, Publ. Alan R Liss Inc, New York, 1985; and Ataxia-Telangiectasia. Eds. Gatti RA and Painter RB, Vol 77. NATO ASI Series. Publ. Springer-Verlag. Heidelberg. 1993).

Scientific Director of the A-T Medical Research Foundation since it was founded in 1984 and chair of the scientific advisory board. Played a role in the early development of A-T parents organizations in England, France, Italy, Norway, and Australia, each of which now funds A-T research in their respective countries. Honors: 1) Jeffrey Modell Lifetime Achievement Award (1992), 2) ATMRF Achievement Award (1995), 3)Ralph Abercombrie Memorial Award for Research in Genetics (1998).

 

 

CLINICAL

In 1987, I established a diagnostic Molecular Pathology laboratory at the UCLA Medical Center in order to apply molecular biology techniques to the analysis of DNA. Working at first with the bone marrow transplantation program (one of my early interests) to identify chimerism in the bone marrow of transplant recipients, this lab now performs an impressive array of diagnostic tests, including fragile X, B/T leukemia/lymphoma cell gene rearrangements, cystic fibrosis, genetic identification (i.e., paternity or mislabelled specimens), Rh testing of amniotic fluid cells, MEN IIA mutations in the Rett gene, radiation sensitivity, Friedreich ataxia, Factor 5. Each of these tests either reduces clinical turn-around time or is not available elsewhere in the clinical laboratory armamentarium. For example, we offer a clonogenic radiosensitivity assay for diagnosing A-T that is not offered anywhere else in the world. We provide prenatal testing for A-T and Nijmegen Breakage Syndrome by chromosomal haplotyping. We were the first to perform such testing, in 1993. Dr. Wayne Grody directs this clinical service. I see patients with ataxia-telangiectasia from all over the world and consult with physicians by telephone on additional families.


 

CONFERENCE PARTICIPATION (1995-1999)

(* = invited speaker)

1/95* First Clinical Conf on Ataxia-Telangiect (Chicago)

3/95* Immunodef of Genetic Origin (Madrid, Spain)

5/95* Europ Conf Human Genetics (Berlin, Germany)

6/95* Davide De Marini Foundation (Rome, Italy)

10/95* NCI Conf on Cancer risk in A-T carriers (Bethesda)

12/95* Am Soc Hum Genet (Minneapolis)

12/95* Seminar. Univ Costa Rica (San Jose)

4/96* Rad Res Soc (Chicago)

4/96* AT Children's Project (Chicago)

6/96* Med Genetics (San Giovanni Rotunda, Italy)

6/96* Seminar. Univ Rome (Rome, Italy)

10/96* Primary immunodeficiency disorders. World Health Organization (Bristol, UK)

2/97 Hum Genome Org (HUGO) (Toronto)

2/97* Amer Assoc Immun (San Francisco)

5/97* Amer Ped Soc/Soc Ped Res (Washington)

8/97* AT Children's Project (Baltimore)

8/97* ATProject (Austin)

9/97* Mexico Soc of Genetics (Encinada)

11/97* Intl Rad Biology (Kyoto, Japan)

11/97* Atomic Bomb Inst (Hiroshima,Japan)

11/97* Seventh International A-T Workshop (Clermont-Ferrand, France)

4/98* Seminar. Univ Mississippi (Jackson)

4/98 Amer Assoc Cancer Res (New Orleans)

4/98 FASEB (San Francisco)

6/98* Primary immunodeficiency disorders.World Health Organization (Vienna)

10/98* Seminar. Bogazici Univ Conf (Istanbul, Turkey)

10/98 Eur Soc Immunodeficiency (Rhodes, Greece)

10/98* Tenth Intl Pediatric Conf (Tehran, Iran)

2/99* DNA Repair. Gordon Conference (Ventura, CA)

2/99* Eighth Intl Workshop on A-T (organizer)(Las Vegas)

9/99* Seminar. Henry Ford Hospital Symposium (Detroit)

10/99* Amer Soc Hum Genet (San Francisco)

10/99 Neuroscience Annual Meeting (Miami)

11/99* AT Project (Austin)