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Noah Craft, MD, PhD, DTM&H 


 

Background

Dr. Craft attended Brown University and then after working as a technician at UCSF in San Francisco, attended UCLA for medical school and graduate school. His PhD research was performed in the lab of Charles Sawyers and was focused on the molecular biology of prostate cancer progression. He completed his dermatology residency at UCLA in the STAR program. There, he completed his post-doctoral research in the laboratory of Jeffery F. Miller in the Department of Microbiology, Immunology, and Molecular Genetics at UCLA working on Listeria monocytogenes as a model to study host immunity against Leishmaniasis and melanoma. During medical school, Dr. Craft developed an interest in tropical medicine and parasitology. He completed an externship at FIOCRUZ in Rio de Janeiro, Brazil. In 2005, he completed the Diploma in Tropical Medicine and Hygiene at the London School of Hygiene and Tropical Medicine. His clinical interests include tropical dermatology and the development of visual medicine diagnostic and training tools for clinicians.  Dr. Craft is the course chair for general dermatology at Harbor-UCLA and the dermatology residency program associate program director.  He is broadly focused on caring for the underserved and on studying diseases that disproportionally affect the world's poorest countries.

Laboratory Research

Dr. Craft’s laboratory research focuses on problems of host immunity and immunomotherapeutics. Specifically, his group is interested in two broad disease areas: Leishmaniasis and malignant melanoma. Both of these diseases fall under the broad umbrella of “insufficient host immunity”. In the case of melanoma, the host does not recognize the cancer as foreign and therapies designed to overcome tolerance to self antigens will ultimately lead to rejection of the melanoma and clearance of the tumor. In the case of Leishmaniasis, an intracellular protozoan parasite found throughout the tropics, the pathogen manipulates host immunity to inhibit what should be natural recognition of a foreign pathogen and thus the host does not mount an effective immune response to clear the parasite. Therapies to disrupt the parasite manipulation of host immunity or to induce the proper anti-parasitic immune response will ultimately lead to clearance of the parasite. For both diseases, we utilize the intracellular bacteria Listeria monocytogenes to induce a powerful host TH1 type immune response. We have created various recombinant Listeria strains that secrete either self antigens from melanoma or parasitic antigens from Leishmania. Thus, the natural immune response to the intracellular bacteria results in a lasting CTL memory response against the bacteria and the recombinant antigens simultaneously. In mouse models of melanoma, we have recently shown that this response is capable of partial protection against metastatic melanoma. Additionally, we have shown that the Toll-like receptor 7 agonist, imiquimod, is capable of enhancing the vaccine induced protective effects. Both of these findings have recently been extended to show effectiveness against intracranial melanoma metastases in the mouse model. Current work is focused on development of recombinant Listeria strains targeting melanoma antigens for eventual use in humans with brain tumors or metastatic melanoma. Additionally, studies to determine the mechanism responsible for the imiquimod induced effects are underway. In mouse models of visceral Leishmaniasis, we are currently testing prospective Leishmania antigens for vaccine effectiveness utilizing the recombinant Listeria model. Additional studies in the laboratory are aimed at understanding the pathogenesis of and host immunity to Leishmaniasis. Another project is focused on using killed but metabolically active parasites as "zombie vaccines" to protect against future Leishmania infections.  Our laboratory is also interested in development of improved disease models through bioluminescent imaging. Using recombinant firefly luciferase, we can detect melanoma and Leishmania in live mice using supercooled CCD detectors (see figures below).

Clinical Research

Dr. Craft’s clinical research focuses on cutaneous and systemic immunomodulation and therapeutics against cancer and infections.  Currently enrolling clinical trials include the use of topical immunomodulators against primary high risk melanoma.  Additionally, in collaboration with Loren Miller, he is studying the etiology of cellulitis and ways to improve diagnostic accuracy in primary care settings using the visually based decision support tool called VisualDx.

Current Lab Members:

Kevin Bruhn, PhD (Co-Director)

Marie Crisel Erfe, MD (UERMMMC Philippines)

Ana Cláudia Maretti Mira, PhD (FIOCRUZ Brazil)


 

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Computerized Diagnostic Support 

Dr. Craft is the Chief Scientific Officer at Logical Images, Inc. In collaboration with many other clinicians in Dermatology, Infectious Disease, and Public Health, we have designed a point-of-care diagnostic and training system to assist clinicians with medical cases that have a visual component to them. VisualDx is a powerful decision support software tool that contains over 25,000 digital images covering over 1200 diseases and can be used to help clinicians answer the question “what is this?” when it comes to rashes and other skin problems, eye problems, problems of the mouth, x-rays, diseases acquired in tropical or international locations, or bioterrorism. Multiaxial cross referencing allows clinicians to input multiple factors including lesion morphology, skin type, immunosuppression, other symptoms, or location of travel to aid in diagnosis. Early detection of infectious disease outbreaks or bioterrorism events will depend on the astute clinician. Dr. Craft also used VisualDx in a clinical trial of inpatients at Harbor-UCLA to determine how it could help improve the 30% diagnostic error rate of cellulitis.  VisualDx is a diagnostic Clinical Decision Support system designed to improve recognition of both rare presentations of common diseases and the expected presentation of rare diseases. Our editorial board and a demonstration of the VisualDx system can be found at http://www.visualdx.com   .

We have also designed a free computerized system called Skinsight for patients to use to help with many of the common skin problems .

Skinsight also contains an area for medical students and professionals. Click here for the self-paced module Rash, rashes, and the art of skin diagnosis   .

Logical Images has also been instrumental for the digital archiving of the late Dr. Victor Newcomer’s collection of over 40,000 Kodachrome slides of skin disease taken over his entire career. Dr. Newcomer donated this enormous collection to UCLA and digital archival of the collection will allow permanent preservation leading to easier utilization of these images for teaching.  A grant from the Dermatology Research Foundation has assisted in this work.

 

Recent Publications:

1.     Craft N, Bruhn KW, Nguyen BD, Prins R, Liau L, Collisson EA, De A, Kolodney MS, Gambhir SS, and Miller JF.  Bioluminescent imaging of melanoma in live mice.  Journal of Investigative Dermatology 2005 Jul;125(1):159-65.

2.     Bruhn KW, Craft N, Nguyen BD, Yip J, De A, Gambhir SS, and Miller JF.  Stimulation of Anti-Self CD8 T Cell Responses and Tumor Protection Following Immunization with Recombinant Listeria monocytogenes Expressing the Murine Melanoma Antigen TRP-2. Vaccine 2005 Jul 21;23(33):4263-72.

3.     Craft N, Bruhn KW, Nguyen BD, Prins R, Lin JW, Liau L, and Miller JF.   The Toll-like receptor 7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine. Journal of Immunology.  2005 Aug 1;175(3):1983-1990.

4.    Prins RM, Bruhn KW, Craft N, Lin JW, Kim CH, Odessa SK, Miller JF, and Liau LM.  CNS Tumor Immunity generated by a recombinant Listeria monocytogenes vaccine targeting TRP-2 and real time imaging of intracranial tumor burden. Neurosurgery.  2006 Jan;58(1):169-78; discussion 169-78.

5.    Prins RM, Craft N, Bruhn KW, Khan-Farooqi H, Koya R, Stripecke R, Miller JF, and Liau LM.  The Toll-like receptor-7 agonist, imiquimod, enhances dendritic cell survival and promotes self tumor antigen-specific T-cell priming: relation to CNS anti-tumor immunity.  Journal of Immunology.  2006 Jan 1;176(1):157-64.


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Los Angeles County Harbor-UCLA Medical Center
Department of Dermatologyy
1000 W. Carson Street, Box 25
Torrance, California 90509