PHLBI Research
On May 27, 2005, the Punch Worthington Research Laboratory was dedicated at the UCLA Medical School in Los Angeles, California. Under the direction of Dr. Robert Cameron, Staff Research Associate Dongmei Hou, MD, Ph.D (see bio below) has embarked on several projects for the treatment and prevention of malignant pleural mesothelioma.
The following are some of the “works in progress” at the Punch Worthington Research Laboratory at UCLA as described by Robert Cameron, MD:
Anti-Angiogenic Drugs (ann-gee-oh-jen-ik): Anti-angiogenic drugs are substances that inhibit new blood vessel formation, and it is exactly this new blood vessel formation that is critical for tumor growth — it’s the tumor’s food supply.
If cancers can’t access a reliable supply of nutrients via new blood vessels, then they can’t grow larger than a few millimeters (1/8 of an inch) in diameter and, consequently, they usually can’t kill people. Inhibition of new blood vessel formation offers an exciting new way to treat cancers, but unfortunately, more research is needed in order to determine precisely how to use these substances in a successful way. There are no reliable methods to monitor treatment effects so that therapy can be personalized for individual patients based on their biologic response to this novel treatment. Furthermore, these drugs may be most useful in chronic “maintenance” therapy regimens because of their low toxicity and modest effect.
To date, use of anti-angiogenic agents is like a shot in the dark: a drug is given and there is no way to assess the immediate success of the treatment until usually 6 to 12 weeks later when a follow-up CT scan is obtained. Ideally, a simple test (i.e., like a urine test) that monitors therapy on a daily and/or weekly basis is needed in order to customize the amount of the drug to each individual patient.
INTERFERON ALPHA-2b (in-ter-feer-on): The body’s immune system naturally produces chemical messengers known as interferons, in response to infections, such as viral illnesses. One type of interferon, called interferon alpha, in particular, helps to fight infections inside cells (such as viral infections) which cause cells to be abnormal (much like cancer cells), helps to stimulate the immune system in general, directly slows tumor growth, and also serves to stop new blood vessel formation (angiogenesis). Preliminary data on using interferon alpha as daily “maintenance” therapy suggests that it may help patients with mesothelioma live for extended periods of time while simultaneously causing few, if any, side effects. Unfortunately, interferon alpha can be given only as a daily or weekly injection, but in the future oral medications may be able to accomplish the same things.
ANTI-INFLAMMATORY DRUGS: Mesothelioma typically occurs from 15 to 40 years or more following asbestos exposure. This is likely due to chronic inflammation (a common theme in many cancers) caused by the long-term exposure of the body (lung and pleura) to asbestos fibers. This raises the possibility that if the inflammation in asbestos-exposed patients can be decreased or eliminated, tumors, such as mesothelioma and even lung cancer could be prevented. Tumor prevention is much more likely to be successful than treatment of tumors once they have already occurred. In order to test this approach asbestos-exposed individuals who are at high risk for developing asbestos-related cancers, such as mesothelioma, need to be carefully screened and followed for signs of disease while receiving medications that reduce inflammation. You could call it a “pre-emptive” strike. One such target drug is Celebrex®, an existing FDA-approved anti-inflammatory compound as well as other existing drugs, such as ibuprofen (Advil®, etc), naproxen (Aleve®), and even possibly something as simple as aspirin. This kind of research requires not only a fairly hefty budget but also the ability to monitor the health details of many individuals over an extended period of time, something that requires the use of a readily available and easy-to-use database. The development of such a database (registry) is already an ongoing project at the Pacific Heart, Lung, & Blood Institute (see below).
PATIENT REGISTRY AND TISSUE BANK: Perhaps the biggest handicap in discovering and/or developing new approaches to mesothelioma and other asbestos-related cancer is the almost complete dearth of information on the characteristics of the disease, current therapies, and treatment outcomes. In order to improve our current understanding and to develop novel future treatments, much better and more detailed information is desperately needed. Two types of information are both critical. First, data about the current nature of the disease, pathology, treatment, side effects, outcomes, and unique patient factors all of which are absolutely essential and able to be abstracted anonymously from medical records. Secondly, tissue samples are vital. Whenever surgery or even diagnostic biopsies are done all over the world, most of the valuable tissue is simply stored in a cell bloc or on a slide and then forgotten or neglected.
In order to combat the scientific lack of knowledge, we hope to collect as much health/medical information as possible from all patients with asbestos as well as other occupational exposures and/or malignant tumors. This information will be stored in an International Mesothelioma Registry. The Registry will include groups of high-risk individuals, such as Navy Veterans, Union Laborers, Miners, and residents of naturally-occurring high-risk areas for asbestos exposure. Furthermore, blood, urine, and tissue specimens (if available) need to be collected to make the health data more meaningful and the research possibilities endless. However, this cannot be done without the help of patients worldwide. A confidential internet website is scheduled to be up and running in early 2009, giving patients the opportunity to sign up to support this project, and even sign a research consent online. With detailed (but anonymous) use of health information and blood, urine, and tissue specimens, scientists should be able to better study, understand, and treat occupational-related diseases.
INTERLEUKIN-4 Toxin (in-ter-loo-kin): Mesothelioma cells (like many cancer cells) have certain unique molecules on their surface which are targets for potential cancer therapies. One of these is a “receptor” for a molecule called interleukin-4 (IL-4). This molecule helps stimulate the body’s immune system but for some unknown reason, the number of receptors on mesothelial cells (including those on mesothelioma) are dramatically increased relative to almost all other cells in the body. One may take advantage of this by creating a toxic molecule that includes the IL-4 molecule (done already by researchers at the National Institutes of Health) to help it bind to the target cells. This creates a poison that specifically binds to tumor cells but only minimally attaches to normal cells. With this direct binding, it is best (and probably least toxic) to use the toxin during surgery at a time when it can be exposed to all the remaining tumor cells in the body, or by injection into a localized tumor nodule. I have conducted experiments which have shown that this toxin can control tumor nodules in mice very consistently in a high percentage of cases. The application of this toxin to humans with mesothelioma is only a short time away.
Dongmei Hou, Ph.D., M.D
Staff Research Associate
Punch Worthington Research Laboratory
Center for the Health Sciences, Room 64-123
David Geffen School of Medicine
10833 Le Conte Avenue
Los Angeles, California 90095-1741
Phone: (310) 206-7015
E-mail: dongmeih@ucla.edu
Education
| August 2004-December 2006 | Postgraduate Researcher Department of Anesthesiology David Geffen School of Medicine University of California at Los Angeles (UCLA) |
| April 1999-March 2003 | Ph.D. Degree in Medical Science, Doctoral Fellow Department of Physiology Gunma University School of Medicine, Japan |
| October 1998-March 1999 |
Visiting researcher, Doctoral Fellow |
| August 1992-October 1998 | Fellow Department of Otolaryngology Dalian Medical University, China |
| September 1987-July 1992 | M.D. Degree Dalian Medical University, China |
Professional Experience
| December 2006 – Present | Staff Research Assoc. Department of Surgery Division of Thoracic Surgery David Geffen School of Medicine University of California at Los Angeles (UCLA) |
| August 2004 – December 2006 | Postgraduate Researcher Department of Anesthesiology Division of Molecular Medicine David Geffen School of Medicine University of California at Los Angeles (UCLA) |
| August 1992 – October 1998 | Physician Department of Otolaryngology The Second Affiliated Hospital Dalian Medical University, China |
Expertise
Physiology: Patch-Clamp technique, Cut-Open Oocyte Vaseline Gap voltage clamp intracellular recording, extracellular recording, data analysis by using various soft wares
Developmental Biology: Immunohistochemistry, Immunofluorescence, Confocal microscopy, Deconvolution microscopy, in situ hybridization, cell culture, make a new construct.
Embryology: Micromanipulation, Embryo collection and culture, Immunosurgery
Molecular Biology: Recombinant DNA, PCR and RT-PCR, Sequencing, in vitro transcription, Northern blot
Cell Biology: Primary cell culture, Cancer cell culture, Subculture, Transfection, Proliferation assay, Apoptosis assay
Biochemistry: Western blot, Two-dimension gel, Isoelectric-focusing gel, Immunoprecipitation
Surgery: Rehabilitation surgery, Facial Plastic Surgery, Micro vascular Surgery, Laryngology, and Neuro-otology
Journal Publications
1. Dongmei Hou, Kazuhiro Suzuki, William J. Wolfgang, Catherine Clay, Michael Forte, and Yoshiaki Kidokoro (2003) Presynaptic Impairment of Synaptic Transmission in Drosophila Embryos Lacking Gsα. The Journal of Neuroscience 23(13):5897-5905.
2. Masaki Sone, Emiko Suzuki, Mikio Hoshino, Dongmei Hou, Hiroshi Kuromi, Masaki
Fukata, Shinya Kuroda, Kozo Kaibuchi, Yo-ichi Nabeshima and Chihiro Hama (2000) Synaptic development is controlled in the periactive zones of Drosophila synapses. Development 127, 4157-4168
3. Dongmei Hou, Jingwei Qi (1995) Clinical Study of 118 Pediatric laryngitis. Journal of Clinical Otorhinolaryngology (Now named as Journal of Clinical Otorhinolaryngology Head and Neck Surgery) 9(12), 13-14
4. Jingwei Qi, Dongmei Hou (1994) The Effects of Fiblaryngoscope in the Diagnosis and Treatment of Laryngeal Disease. Dalian Medical College Journal of Medicine (Now named as Dalian Medical Journal) 16(4)286-288
5. Daniel Sigg, Dongmei Hou, Riccardo Olcese (2007) Permeation in Large and Small Conductance K+ Channels Probed by Temperature and Viscosity Sensitivity. Submitted to Biophysical Journal. Daniel Sigg and Dongmei Hou contributed equally to this work.
Book Chapters
1. Dongmei Hou (2002) “Frozen Cosmetology” in “21st Century Medical University Teaching: Physical Therapy and Gymnastic Cosmetology” Zaien Hou, Jingwei Qi and Ming Guo, eds. Science Press China (ISBN: 7-03-010652-0/R.911), China, pp, 54-65.
2. Zhenzi Wang, Dongmei Hou, Jiamei Hou (2002) “Fumigation Cosmetology” in “21st Century Medical University Teaching: Physical Therapy and Gymnastic Cosmetology” Zaien Hou, Jingwei Qi and Ming Guo, eds. Science Press China (ISBN: 7-03-010652-0/R.911), China, pp, 66-84.
3. Jingwei Qi, Dongmei Hou (2002) “Common Beauty of Fitness Training Methods” in “21st Century Medical University Teaching: Physical Therapy and Gymnastic Cosmetology” Zaien Hou, Jingwei Qi and Ming Guo, eds. Science Press China (ISBN: 7-03-010652-0/R.911), China, pp, 243-249.
4. Qun Ai, Dongmei Hou, Na Sun, Jie Bai, Zaien Hou (2002) “Acupuncture Cosmetology” in “21st Century Medical University Teaching: Meridian Cosmetology” Zaien Hou and Jingwei Qi, eds. Science Press China (ISBN: 7-03-010652-0/R.911), China, pp, 9-101.
5. Jingwei Qi, Yuzhen Hou, Qun Ai, Xia Zhao, Dongmei Hou (2002) “Massage Cosmetology” in “21st Century Medical University Teaching: Meridian Cosmetology” Zaien Hou and Jingwei Qi, eds. Science Press China (ISBN: 7-03-010652-0/R.911), China, pp, 103-157.
Conference Presentations
1. Dongmei Hou, Riccardo Olcese (2006) A Functional Salt Bridge in BKCa Channel Outer Pore? Biophysical Society, 2006 Annual Meeting, USA
2. Dongmei Hou, Riccardo Olcese (2006). Structural Diversity in K+ Channels Outer Pore. American Society of Anesthesiologists, 2006 Annual Meeting, USA
3. Dongmei Hou, Daniel Sigg, Riccardo Olcese (2006). Permeation properties of BK and Shaker K+ Channels. American Society of Anesthesiologists, 2006 Annual Meeting, USA
4. Dongmei Hou, Riccardo Olcese (2005) A Functional Salt Bridge in BK Channel Outer Pore? The Brain Research Institute at UCLA, Seventeenth Annual Neuroscience Poster Session, USA
5. Dongmei Hou, Kazuhiro Suzuki, Michael Forte, and Yoshiaki Kidokoro (2002) Impairment of Synaptic Transmission in Drosophila Embryos Lacking Gsα. The 25th Annual Meeting of Japanese Neuroscience Society, Japan
6. Dongmei Hou, Hiroshi Kuromi, Yoshiaki Kidokoro (2000) Effects of Veratridine on the Presynaptic Function at Drosophila Neuromusculat Junctions. The 23rd Annual Meeting of Japanese Neuroscience Society, Japan
7. Dongemi Hou, Jingwei Qi (1997) Livostin Treatment of Allergic Rhinitis Analysis. 5th National Otorhinolaryngology Clinic Progress Symposium on the New Compilation, China
8. Dongmei Hou, Jingwei Qi (1996) The Comprehensive Diagnosis and Treatment of the Serious Acute Epiglottitis. The 4th Annual Meeting of Chinese Clinical Otorhinolaryngology Society, China
9. Dongmei Hou, Jingwei Qi (1995) Diagnosis and Treatment of Pediatric Laryngitis. The 3rd Annual Meeting of Chinese Clinical Otorhinolaryngology Society, China
10. Daniel Sigg, Dongmei Hou, Riccardo Olcese (2006). Temperature and D2O as discriminators of permeation mechanisms in BKCa and Shaker Channels. Predictions of a 4-state Cyclic Model. Biophysical Society, 2006 Annual Meeting, USA
11. Nicoletta Savalli, Dongmei Hou, Riccardo Olcese (2006). Ca2+ and Voltage Dependent Conformational Changes in BKCa Channel Biophysical Society, 2006 Annual Meeting, USA
12. Nicoletta Savalli, Dongmei Hou, Daniel Sigg, Riccardo Olcese (2006). Ca2+ Dependent Conformational Changes in Human Large Conductance K+ Channels (BK) During Activation. American Society of Anesthesiologists, 2006 Annual Meeting, USA
13. Daniel Sigg, Dongmei Hou, Riccardo Olcese (2005) Maximum Ion Throughput Across Small Free Energy Barriers in the Large-Conductance BKCa Channels: Evidence from Temperature and D2O Experiments. American Society of Anesthesiologists, 2005 Annual Meeting, USA
14. Daniel Sigg, Dongmei Hou, Riccardo Olcese (2005) Maximum Ion Throughput across Small Free Energy Barriers in the Large-Conductance BK Channels: Evidence from Temperature and D2O Experiments. The Brain Research Institute at UCLA, Seventeenth Annual Neuroscience Poster Session, USA
15. Jingwei Qi, Dongemi Hou (1997) Kang Nose in the Treatment of Rhinosinusitis Clinical Observation. 5th National Otorhinolaryngology Clinic Progress Symposium on the New Compilation, China
16. Taleh Yusifov, Nicoletta Savalli, Dongmei Hou, Nigar Yusifova, Riccardo Olcese (2007) Ca2+-Induced Conformational Changes in the RCK2 Domain of hSlo BKCa Channel
Biophysical Society, 2007 Annual Meeting, USA
17. Nicoletta Savalli, Taleh Yusifov, Dongmei Hou, Daniel Sigg, Riccardo Olcese (2007) Mutation in the “Ca2+ Bowl” abolishes the coupling between Ca2+ activation and S4 movement in BKCa channels. Biophysical Society, 2007 Annual Meeting, USA
18. Roshni Vyas, Nicoletta Savalli, Dongmei Hou, Sarah Buxton, Riccardo Olcese (2005) Ca-Dependent Conformational Changes in BKCa channels. The Brain Research Institute at UCLA, Seventeenth Annual Neuroscience Poster Session, USA
19. Masaki Sone, Emiko Suzuki, Mikio Hoshino, Hou Dong Mei, Hiroshi Kuromi, Masaki Fukata, Shinya Kuroda, Kozo Kaibuchi, Yo-ichi Nabeshima, Chihiro Hama (1999) Localization and possible function of cell adhesion molecules and the Still life – Rac-pathway in the synapses. Japanese Drosophila Research Conference 4th Workshop
Membership in Professional Associations
- Member, Biophysical Society, 10/2005-present
- Associate chairman of the executive council, International Cosmetology Medical Education Association (ICME), 7/2004-present
- Member, Japanese Neuroscience Society, 1999-2003
- Member, Chinese Medical Association, 1992-1998