Jump to content

Dr. Joseph Lorenzo

  • Content Count

  • Joined

  • Last visited

  • Days Won


Everything posted by Dr. Joseph Lorenzo

  1. This installment of my blog is its final chapter. For almost six years I have had the privilege of being able to write about the world of bone and mineral research in these pages. I hope that you, the readers, have been happy with the results. It has been a great honor for me to write these blogs. I very much thank the ASBMR, its officers and its administrators for being so generous in allowing me essentially free reign to choose and expound about topics that I feel are important to ASBMR members. Since 2010, I have written about 75 blogs. When I first started, I tried to be somewhat
  2. Funding is the bedrock of all biomedical research. In the United States there are a number of agencies that support scientific biomedical research. However, far and away the largest single source is the National Institutes of Health (NIH). Since 2003 funding for the extramural program of the NIH has declined in inflation-adjusted dollars by 22% (see Figures 1 and 2, which were created by Federation of American Societies for Experimental Biology, FASEB). In turn, this decrease in inflation-adjusted support has decreased the number of research project grants that NIH can fund in any given yea
  3. Osteoporosis is a disease with a strong genetic etiology (1). However, exactly which or how many genes are involved in the pathogenesis of this condition is unknown. Numerous studies have tried to link specific regions of the genome to traits such as bone mineral density to understand the genetic variations that predispose individuals to osteoporosis. In the past these have either used a genome wide association study (GWAS) approach or a candidate gene approach. GWAS uses single nucleotide polymorphisms (SNPs) or variations in DNA, which occur naturally throughout the genome, to identify r
  4. Diabetes is a common condition with significant morbidities (1). The World Health Organization estimates that the number of diabetics increased from 85 million in 1985 to 217 million in 2005 and may reach 366 million by 2030. It is a major cause of cardiovascular, renal, neurologic and ophthalmologic diseases. In the United States the cost of diabetic care is projected to reach almost 200 billion dollars by 2020. Type 2 diabetes, which has in the past was called non-insulin dependent or adult onset, is the most prevalent form, comprising at least 90% of the cases. Because the incidence of
  5. While members of the ASBMR generally study bones to learn about the function of their cells or the ways in which their structure and mechanical properties are altered in health and disease, paleontologists and archeologists study fossilized bones to glean information about ancient animals and humans. Until thirty-five years ago, knowledge about ancient species was limited to what could be obtained from the morphology of their bones or the location where the specimens were found. However, advancements in molecular biology and, especially, in DNA sequencing have revolutionized the amount of inf
  6. Aging is a complex process, which was once considered inevitable and irreversible. However, studies in mice, using heterochronic parabiosis, argue that some effects of aging may, in fact, be reversible. In this model the vascular system of a young mouse is connected to the vascular system of an aged mouse. These studies have been particularly informative about the role that aging has in the response to injury. In 2005 Conboy et al. (1) found that delays in the regenerative potential of muscle stem (satellite) cells and liver hepatocytes in aged mice could be reversed when these animals wer
  7. The reproducibility of published data remains a critical determinant of the quality of any research. Unfortunately, some scientific articles are published and subsequently their results are found to be difficult or impossible to reproduce. When this occurs, it affects all scientists because it erodes the public’s trust in science and scientists. The majority of recently disputed articles have concerned preclinical or basic science topics. In response to this issue, Francis Collins, the Director, and Lawrence Tabak, the Principal Deputy Director, of the US National Institutes of Health wrote
  8. In a previous blog, I highlighted the ease with which CRISPR/Cas9 technology could be used to edit DNA sequences in almost any cell (1). At my institution the gene targeting and transgenic mouse facility is exclusively using CRISPR/Cas9 to engineer its mouse models and I suspect the same is true at any number of centers around the world. The advantage of this technology is that genetically manipulated mice can be created in half the time and at almost half the cost of the previous technology, which employed homologous recombination in embryonic stem cells. CRISPR/Cas9 also eliminates the ne
  9. Steven M Krane, M.D., a founding member of the American Society for Bone and Mineral Research and its 4th President passed away on January 19, 2015 at age 87 after a long illness. Steve was a giant in our field whose contributions to both skeletal biology and rheumatology are immeasurable. He was originally from New York City, where he received both his undergraduate and medical degrees at Columbia University. However, he began his long affiliation with the Massachusetts General Hospital and Harvard University directly after his graduation from Columbia’s College of Physicians and Surgeons.
  10. Most available therapies for osteoporosis function as inhibitors of bone resorption. However, in patients with very low bone mass or those who already have a fragility fracture, anabolic therapies, which enhance bone formation, may be more effective (1). Currently, only analogs of parathyroid hormone are approved as bone anabolic agents to treat osteoporosis. The discovery that the canonical Wnt beta-catenin signaling pathway stimulates bone formation has identified a number of new drug targets, which may be exploited to develop novel anabolic therapies for osteoporosis (2). Wnts are signal
  11. Trying to perform significant nutritional research on humans may be the most difficult endeavor that clinical scientists ever attempt (1). Truly meaningful data about the relationship between what we eat and how it affects our health frequently takes many years to produces results. The gold standard of clinical research, the randomized control trial, is very difficult to perform when testing nutritional hypotheses. This is because of the variability in compliance that inevitably occurs when subjects are attempting to maintain a specific diet for long periods and the considerable costs that
  12. The ability to manipulate the genome of bacteria and viruses is now a common tool of experimental biology. More recently, technologies have emerged that allow the development of genetically manipulated animals for use in research and commercial applications. However, until recently, production of genetically manipulated animals was an expensive and laborious process that relied on spontaneous homologous recombination in embryonic stem cells. It was not unusual for the cost of this technology to exceed $20,000 and the process to take over 12 months to complete. In the past few years, te
  13. Most medical research is funded by either government or philanthropic organizations. The vast majority of these make their funding decisions based on a rigorous peer review of the scientific merit of a specific project. In the United States the National Institutes of Health (NIH), by far the largest source of funds for biomedical research, dispenses over 30 million dollars each year. The majority of grant proposals to the NIH are reviewed on a multipoint scale, which examines both the project and the investigator. However, for most of these it is the merits of the proposed project that car
  14. Vitamin D is essential for bone health. However, significant controversy exists about which technology should be used to assays vitamin D levels in serum, what values constitutes evidence of insufficiency and whether vitamin D levels should be routinely determined in the general population as part of a preventative screening program. In 2010 an Institute of Medicine (IOM) panel issued guidelines, which stated that most adults 18 to 70 years old need to consume 600 IU of vitamin D per day while those older that 70 should consume 800 IU per day (1). The IOM panel also stated that total serum
  15. Bone is a highly vascular organ. It has been known for many years that endochondral bone development coincides with angiogenesis in bone (1). However, the molecular signals that regulate the development of bone and its vascular system and the importance of their interactions for bone development has only recently been appreciated. It is now recognized that bone cells make factors that regulate angiogenesis. Among these, vascular endothelial growth factor (VEGF), a major stimulus of angiogenesis, plays an important role. Additional studies have shown that production of VEGF in a variety of
  16. Biomedical Research in the United States is currently in turmoil over the mechanisms that provide its funding. This is predominantly the result of a contraction in US Federal support for biomedical research when calculated to account for inflation (a 25 percent decrease in real dollar terms since 2003) and a failure by institutions that employ scientists (both academic and non-academic) to anticipate this event. In retrospect, it seems obvious that the continued growth of Federal funding for research, which was rapid from 1998 to 2003, was not sustainable and eventually would end. Now two
  17. Humans have evolved to interact with a microbial world. The total of micro-organisms (bacteria, fungi, protozoa and, possibly, viruses) that cohabitate an individual is termed its microbiota (1). The term microbiome is sometimes used interchangeably with microbiota, although the strict definition of the latter is reserved for a description of the collective genomes of microorganisms in an individual. Because of advances in technology, especially the ability to sequence the genome of all microorganisms that colonize us, we know much more about the diversity of microorganisms in our microbiota
  18. The process of drug discovery to combat human disease is often long and tortuous. Most often the successful development of a therapy relies, first, on the identification of a drug target and, second, on the development of agents, which can manipulate that target to reverse or arrest the course of disease. Drug targets are commonly critical elements of the pathologic process, which can be manipulated without seriously affecting normal human function. In the modern world, the identification of drug targets requires a thorough understanding of the molecular mechanisms of disease and the ide
  19. The ASBMR Educational Resource Center As one of its core missions, the ASBMR is constantly striving to provide its members with comprehensive educational materials. In order to better fulfill this goal, it recently launched an Education Resource Center web page (1). This page is a single site that provides an extensive array of both basic and clinical educational materials that are relevant to members. As it develops, the site will become the repository for all ASBMR online educational content. This will include web videos and printed summaries of ASBMR-sponsored educational symposi
  20. Adequate vitamin D levels are essential for bone health (1) and may influence any number of other organ systems. Vitamin D in the strictest definition is not a vitamin, since it can be made in the skin under the influence of ultraviolet radiation and hence, is not an essential nutrient. Rather, it is best thought of as a hormone since its most active metabolite (1, 25 (OH)2 vitamin D) is produced, for the most part, in the kidneys by a highly regulated mechanism and then acts throughout the body. Pigmentation can filter the ultraviolet radiation that converts provitamin-D (7 dehydrocholeste
  21. There are many types of people who have great impact on our professional lives. Some are the scientific leaders in our field, who often run large research groups, mentor us during the initial periods of our career and, frequently, have their work highlighted at national meetings or in journal perspectives. Others are very different. These are the people who work behind the scenes with grace and diligence to support the mission of funding agencies, scientific societies and journals that are essential for scientific research. Priscilla Chen was in the latter group. Unfortunately, Priscilla d
  22. As most scientists know, biomedical research is critically dependent on stable sources of funding. Research technicians, students and post-doctoral fellows, who typically perform the majority of the work in a laboratory, often take many years to master the complex technologies that are the heart of any successful research operation. Hence, it is essential that their level of expertise be maintained and seamlessly passed on to the next generation, in order that the work of a lab can efficiently continue. To preserve this expertise and maintain productivity, scientists need to regularly secur
  23. The New York Times recently published an article (1) describing concerns about protecting the privacy and interests of the individuals who provide biologic samples for scientific research. The article revolves around two recent publications by researchers in Europe and the United States (2, 3) who detailed the complete genomic sequence of HeLa cells. As explained in a best-selling book, The Immortal Life of Henrietta Lacks, by Rebecca Skloot (4), HeLa cells are derived from a cervical cancer that was removed from a 31-year-old woman, Henrietta Lacks, in 1951. They are a milestone in human b
  24. The control of serum calcium within a tightly defined range is essential for the normal function of all mammals. Consequently, a sensitive system of calcium sensors and regulatory hormones has evolved to maintain serum calcium within a relatively narrow range. Central to this endocrine system is the sensing of serum ionized calcium by the calcium sensing receptor (CSR). This, in turn, leads to the production of second messengers by enzymes like phospholipase C-β (PLC-­β) and the subsequent regulation of parathyroid hormone, the critical endocrine hormone for maintaining normal serum calcium
  25. Science is a field that revolves around quantification. Scientists spend much of their time utilizing technologies to quantitate natural events in order to determine if the manipulation of those events alters them. Hence, it is not unexpected that scientists, when evaluating themselves or their peers, frequently employ numeric metrics. In recent years such measures have often been applied to the productivity of individual scientists. There are numerous ways to measure this productivity but, not infrequently, the quality of a manuscript is evaluated by the Journal Impact Factor (JIF) of whe
  • Create New...