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May 2013 Archive

Posted by Chris on May 9th, 2013  ⟩  0 comments

The Bone Morphogenetic Proteins (BMPs) were first discovered and named by Marshall Urist in 1965 as a mix of proteins that appeared to be responsible for bone regeneration. In the decades since, these cytokines have become one of the most important families of growth factors for therapeutic and medicinal purposes!

There are 20 growth factors that have been named as BMPs, and many are also members of the TGF-β superfamily of proteins, but not all are technically considered “bone morphogenetic proteins” or even directly affect bones. For instance, BMP1 is a misidentified protein with chordinase and procollagen proteinase activities (Kessler, 1996). Several others have no bone related roles at all, such as BMP8 (involved in reproductive cells), BMP10 (involved in cardiac development) and BMP15 (involved in ovarian physiology) (Bessa, 2008). Also, BMP12, 13 and 14 are actually involved in cartilage development, rather than bone development (Bessa, 2008). Typically, only BMP2-11 are actually considered to be true BMPs.

However, even the true BMPs play a wider role in the body than simply bone development. BMP2 has been shown to play a part in heart morphogenesis and in neural stem cells (White, 2001). BMP2 is also involved in the Hedgehog Signaling Pathway and the TGF-β signaling pathway. BMP4 is critical in the development of tooth and limbs and in fracture repair, specifically in endochondral bone formation in humans. It has also been shown to be an important factor in muscle development (Christ, 2002) and ureteric bud development (Michos, 2007). BMP7 is directly responsible for the induction of a wide range of osteogenic genes. It has also been used therapeutically as a treatment for kidney disease and may also be able to treat some forms of infertility. BMP4 and 7 are also directly affected by the Noggin growth factors.BMP Signaling Pathway

BMPs are typically homo or heterodimers linked via disulphide bridges. The BMP2/4 group, BMP7 and some others (BMP9/10 and BMP 12-14) also have over 50% amino acid homology (Bessa, 2008). BMPs form a conserved motif of seven cysteines, which is involved in the formation of six intrachain disulphide bonds and a single interchain bond, necessary to dimer formation (Bessa, 2008). BMPs bind to serine-threonine kinase receptors on the surface of the cell, but only STKI and STKII appear to play significant roles in BMP binding or signaling.

At Goldbio, we have recombinant BMP2, BMP4 and BMP7 available for research, although currently, only BMP2 is a biologically active protein. Our BMP4 and BMP7, while inactive proteins, are still useful in the lab as a means to effectively stimulate antibodies or as controls for Western blots. For more information about these products or any of our products, you can email us at:


Kessler E, Takahara K, Biniaminov L, et al. 1996; Bone morphogenetic protein-1: the type I procollagen C-proteinase.Science 271: 360–362.

Bessa, P. C., Casal, M., & Reis, R. L. (2008). Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). Journal of tissue engineering and regenerative medicine, 2(1), 1-13.

White PM, Morrison SJ, Orimoto K, et al. 2001; Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals. Neuron 29: 57–71.

Michos, O., Gonçalves, A., Lopez-Rios, J., Tiecke, E., Naillat, F., Beier, K., & Zeller, R. (2007). Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development, 134(13), 2397-2405.

Christ, B., & Brand-Saberi, B. (2002). Limb muscle development. International Journal of Developmental Biology, 46(7), 905-914.

Category Code: 79101

Posted by Chris on May 16th, 2013  ⟩  0 comments

Ever since the beginning of our awareness of growth factors in the early 1960’s by Stanley Cohen and Rita Levi-Montalcini, EGF (Epidermal Growth Factor) has been in the forefront of medical science. EGF, along with the EGF Receptors (EGFR), has been implicated in a number of cancer types for decades, although the exact pathway has been elusive. Scientists know that that the interaction between EGF and EGFR creates an intracellular signaling cascade that affects many other growth factors, including FGF2 (Fibroblast Growth Factor 2), IL8 (Interleukin 8) and VEGF (Vascular Endothelial Growth Factor). But that’s also precisely the reason that researchers have had so much trouble pinning down the implicit role that EGFR has on cancer development and proliferation.

EGF is only the founding member of a family of proteins that bear its name. There are 13 known EGF family members, including TGF-α (Transforming Growth Factor-α) and HB-EGF (Heparin Binding EGF-like Growth Factor). EGF family members can be characterized by their association with EGFR. There are 4 EGFRs, which all have multiple names. We will settle on calling them ErbB1, ErbB2, ErbB3 and ErbB4. Of these, ErbB2 does not bind to any of the EGF ligands. Instead, ErbB2 is activated only as a consequence of homodimer formation with one of the other three EGFRs.

Recently, Seshacharyulu et al (2012) published a comprehensive review of EGFRs and the various therapeutic treatments that are currently being investigated that is well worth the read. There are two therapeutic approaches currently being employed: monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs). Monoclonal antibodies are specifically designed to be directed against the extracellular region of EGFR, creating a ligand competitive inhibition (Burgess, 2003). These antibodies then induce receptor internalization, ubiquitinization, degradation and prolonged downregulation (Sunada, 1986). TKI’s exist as adenosine triphosphate (ATP) analogues and inhibit EGFR signaling by competing and binding with ATP binding pockets on the intracellular catalytic kinase domain of receptor tyrosine kinases (RTKs) (Seshacharyulu, 2012). EGFR InhibitionThere are two types of TKI: Reversible inhibitors, which compete with ATP molecules, and Irreversible inhibitors, which bind to kinase active sites covalently (prolonging their effects and decreasing the need for frequent dosing).

Seshacharyulu et al reviewed several of the ongoing cancer therapeutic treatments in their article, including the monoclonal antibodies Cetuximab and Panitumumab as well as the TKIs, Gefitinib, Erlotinib, Lapatinib, and a new generation TKI called Canertinib. Ultimately, the reviewers believe that irreversible TKIs have the best opportunity for cancer treatment, but the risk is that they tend to have too much non-specificity and TK point mutations can easily lead to resistance. But the combined use of a chemotherapeutic TKI with a chemopreventive agent can potentially have an adjuvant action by inhibiting transcriptional factors and intercepting the autocrine loops generated by the activation of EGFR (Seshacharyulu, 2012).

To read the full free article, go to Seshacharyulu et al (2012) on Pubmed. And for questions on EGF or any of GoldBio’s other growth factors, just email us at


Seshacharyulu, P., Ponnusamy, M. P., Haridas, D., Jain, M., Ganti, A. K., & Batra, S. K. (2012). Targeting the EGFR signaling pathway in cancer therapy. Expert opinion on therapeutic targets, 16(1), 15-31.

Burgess, A. W., Cho, H. S., Eigenbrot, C., Ferguson, K. M., Garrett, T. P., Leahy, D. J., ... & Yokoyama, S. (2003). An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Molecular cell, 12(3), 541-552.

Sunada, H., Magun, B. E., Mendelsohn, J., & MacLeod, C. L. (1986). Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proceedings of the National Academy of Sciences, 83(11), 3825-3829.

Category Code: 79101

Posted by Chris on May 23rd, 2013  ⟩  0 comments

It is a still a commonly held belief that nerve damage can never be healed or repaired sufficiently to regain use. But in recent years that dogmatic view has been successfully challenged and refuted by our ever-growing understanding of growth factors, specifically the Neurotrophins, and their relationships with stem cells. Neurotrophins are neuronal factors which are important regulators of neural development, function and survival. Neurotrophins are key components of Neural Stem Cells (NSCs), which are primordial and uncommitted cells that have been believed to give rise to the vast array of more specialized cells of the CNS which are defined by their ability to (1) to differentiate into cells of all neural lineages in multiple regional and developmental contexts; (2) to self-renew; (3) to migrate and populate developing and/or degenerating CNS regions; and (4) to have biofunctional multipotency to mediate systemic homeostasis through capacities such as production of trophic factors, formation of gap junctions, etc. (Teng, 2011).

Since the original discovery of Nerve Growth Factor (NGF) in the 1960’s by Cohen and Levi-Montalcini, the class of neurotrophic factors has grown to just 4 official neurotrophins: NGF, Brain derived neurotrophic factor (BDNF), Neurotrophin 3 (NTF3, and Neurotrophin 4 (NTF4). But the class has also grown to typically include the GDNF (Glial cell-derived neurotrophic factors) as well as the CNTF (Ciliary neurotrophic factor) families of ligands.

NTF ReceptorsNeurotrophins are defined by their expression as well as their neuronal targets, which typically contain an appropriate trk receptor, which are transmembrane tyrosine kinases that specifically bind to neurotrophins. There are 3 trk receptors: trkA, which primarily binds and is activated by NGF; trkB, which binds and is activated primarily by BDNF and TNF4 and to a lesser extent NTF3; and trkC, which binds and is activated by NTF3. There is an additional family of receptors called the P75 neurotrophin receptor, or Low-affinity Nerve Growth Factor Receptor (LNGFR). All 4 of the neurotrophins are known to bind to the LNGFR, though the precise function of the P75 receptor is still not well understood. (For another wonderful general review of neurotrophins (and where I borrowed this great illustration), you should visit Betarhyme.)

Neurotrophins are primarily present in the development of the nervous system and responsible for the initial growth of neurons and the central nervous system. After development, they are also capable of promoting neural cell repair and even neural re-growth; exciting prospects for research projects concerning ALS or even Alzheimer’s. Shen et al. (2010) recently found that NTF4 suppresses the Il6 receptor and the Notch signaling pathway, suggesting an interesting, potential signaling cascade in neurogenesis. Below is their proposed signaling pathway for the differentiation of NSCs into neuronal progenitors.

NTF4 Signaling-Shen 2010

GDNF is another neurotrophic factor that is usually considered to be under the greater family of neurotrophins. GNDF is most notable for its promotion and support of motorneurons and dopamine neurons. The loss of motorneuron populations are complication of neural degradation diseases such as Parkinson’s disease as well as ALS. GNDF primarily binds through GDNF family receptor-α1 (GFRα1), which facilitates the binding of RET molecules, a receptor tyrosine kinase (Ghitza, 2011). RET activation is involved in neuronal survival, differentiation and proliferation, neurite outgrowth, and synaptic plasticity (Sariola and Saarma, 2003).

For more information on these and any of our other products, you can always email us at:!

Teng, Y. D., Yu, D., Ropper, A. E., Li, J., Kabatas, S., Wakeman, D. R., ... & Sidman, R. L. (2011). Functional multipotency of stem cells: a conceptual review of neurotrophic factor-based evidence and its role in translational research. Current neuropharmacology, 9(4), 574.

Shen, Y., Inoue, N., & Heese, K. (2010). Neurotrophin-4 (ntf4) mediates neurogenesis in mouse embryonic neural stem cells through the inhibition of the signal transducer and activator of transcription-3 (stat3) and the modulation of the activity of protein kinase B. Cellular and molecular neurobiology, 30(6), 909-916.

Ghitza, U. E., Zhai, H., Wu, P., Airavaara, M., Shaham, Y., & Lu, L. (2010). Role of BDNF and GDNF in drug reward and relapse: a review. Neuroscience & Biobehavioral Reviews, 35(2), 157-171.

Sariola, H., & Saarma, M. (2003). Novel functions and signalling pathways for GDNF. Journal of Cell Science, 116(19), 3855-3862.

Category Code: 79101

Posted by Patrick on May 13th, 2013  ⟩  0 comments

In a remarkable paper published in the May 9th edition of Cell, two researchers at the Harvard Stem Cell Institute, Richard R. Lee M.D. and Amy Wagers PhD., determined that you can reverse cardiac hypertrophy in older mice by treating them with injections of Growth Differentiation Factor 11 (GDF-11, also known as BMP-11).  Cardiac hypertrophy is the thickening of the heart muscle, and occurs naturally with aging.  While the heart is still beating normally, the amount of blood the heart is able to draw in per beat is reduced, which causes the decrease in function. This condition is known as diastolic heart failure, and is a serious medical condition that many elderly people face.

In previous research performed by Dr. Wagers, using a technique called parabiosis, she had demonstrated that some undetermined factors in the blood of younger organisms could be beneficial to the tissues of older organisms. In parabiotic mice, the circulatory systems of two mice are literally fused together, so both mice are circulating the same blood, a technique which has been around since the 19th century (and seems like something out of a mad scientist fiction novel). Despite the strange technique, the researchers found that if they paired an older mouse exhibiting cardiac hypertrophy with a young mouse with no heart issues, the heart tissue in the older mouse would begin to repair itself, and look almost identical to the heart tissue in the younger mouse. After a few years of studies and a great deal of searching, they were able to determine that the factor responsible for this rejuvenation was Growth Differentiation Factor 11 (GDF-11), also known as BMP-11.

BMP-11 is a member of the TGF-β superfamily, and has been previously shown to regulate the expression of Hox gene. After they isolated BMP-11 as the active factor, the researchers found that they could cause the same rejuvenation simply by injecting the older mice with doses of BMP-11. While there is still a lot of work to do in order to understand the exact effect that BMP-11 plays in this system, the researchers are hopeful that their work can lead to some clinical studies and that BMP-11 will have a similar effect in humans as it does in mice. Here at Goldbio, we feel that as we begin to understand more about growth factors and the different roles they play in cell and tissue biology, that more discoveries like this will be reported, and could lead to life saving cures in the near future. So while Dracula may be “dead and loving it”, due to his penchant for blood, he might just be young at heart.

For more information, see the published paper in the May 9th issue of Cell, and here is a link to an interview with Dr’s Lee and Wagers, from the Harvard Stem Cell Institute YouTube page.

Wagers A., Lee R. et al. “Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy” Cell, Volume 153, Issue 4, 9 May 2013, Pages 828–839

Andersson O, Reissmann E, Ibáñez C. "Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis" (2006). EMBO Rep 7 (8): 831–7.

Category Code: 88221 79101

Posted by unknown on May 30th, 2013  ⟩  0 comments

May is quickly coming to a close and the stresses of finals, presentations and papers are finally a thing of the past as summer graciously presents sunshine and lazy days. However, if you are like me and your senior year is fast approaching, as are the deadlines to apply to graduate school, your plate is probably a little fuller than you would like. As to be a competitive candidate in today's Ph.D. programs we are told to be involved on campus, have a high GPA, volunteer to show your humanities side, and get an outstanding score on the GRE (for which we should have already started studying). While all these things are true, they should also already be finished or nearing completion. In reality, your resume is not going to see a dramatic change before you start applying to programs since applications will be due at the beginning of or before the upcoming semester. For this reason, it is important to focus your efforts on where you will be applying, and to find the school that best suits you. Luckily, there are a few fool-proof ways to sort through all of the suggestions that you have received from family, friends, mentors and teachers and select the program that is right for you.

First, focus on the department rather than the school’s name. When I started applying to be an undergraduate I knew I wanted to major in biology, and everyone was focused on getting into a top 20 school. The name of the university was somehow directly related to how much your parents were going to brag about you to their friends and co-workers. After hearing Harvard or Yale, the “oh, wow” face always followed. Nevertheless, this is not always the case with graduate schools, as the most well-known schools may not necessarily have the program that is right for you. So the first thing to do is to check out the department in which you are interested at your favorite schools, and if you don't already have a list Google is going to be your best friend. Look up each school, and check out all of the mentors in your desired department. Don't stop at simply looking at their picture and the brief summary about their life and research on their lab page. If they are anything like my PI's they will not have touched that page in years. Therefore you really need to dig deep as this person is going to be vital to you in the next few years. So, when I check out a possible mentor I look at their publications in a very in depth way. You need to see how many publications they have, if they are all in a focused area, what journals they are being published in, if their articles are being cited, and the dates on their publications. All of these factors are going to show you if their research is important and current, or if they are in a slump with unexciting or irrelevant research. The last thing you want to do is get stuck in a boring lab where the PI has stopped doing original and cutting-edge research. This is very important to you because publications will factor into whether or not you will be able to graduate. It is also important that you find their research interesting, as it will engulf your entire life for the upcoming years.

The next thing to look at after your potential mentor is the alumni. Pick a few of the most recent graduates and see what they are doing now. It is important to know that you will be able to find a job after you graduate, and at what type of institution. If one program has a varying range of success amongst their graduates, then try to find the mentor. It is possible, and more likely probable, that even within the same department there is going to be a difference in success from mentor to mentor. Therefore the more information you can find out about these people, the more informed you can be in making your decision. However you don't have to stop at the most recent alumni, but also look at some of the older alumni to see how their career was able to develop. If the older alumni are not able to keep up with the growing field, then maybe the program is not very well developed in critical thinking. This is a crucial flaw since science is constantly changing. Therefore it is important to look at the success of the alumni and compare them to your other top schools, since, ideally, in the next few years, your name will be added to this list.

Finally, you need to consider is the local environment. While some people will tell you to ignore the looks of the school and focus entirely on the academics, the fact is that this will be your home for the next 4-7 years. If you do not enjoy the cold, then picking a university in upstate New York is probably not the best idea even if the academics are outstanding. The best thing to do, if you have the time, would be to visit the area with your family before applying. Now, I specified family because taking a road trip anywhere with friends is going to be enjoyable and will not give you a true idea of what the city will be like living there on your own. So, take a weekend to explore what the area has to offer, and if the atmosphere is inviting to you. However, if you are like me and do not have the time to travel around to your top picks, then try to allow time after your interview to explore at least a little bit of what could be your new home. At the end of the day you have to pick both the mentor and location that suits your needs and desires in a grad program as it is your life that will be changed over the course of earning your degree. So no matter who is an alumni there, make sure that the final decision is yours and that you will be happy living with the school that you have chosen.

Deanna Tiek
Vanderbilt Class of 2014
Deanna is an intern at Goldbio this summer.

Category Code: 79108